Application of low-intensity magnetic field combined chemotherapy medicine in tumor treatment

Abstract

The invention discloses an application of a low-intensity magnetic field combined chemotherapy drug in tumor treatment, and belongs to the field of biological medicine, a low-intensity magnetic field environment and a clinically common tumor chemotherapy drug are combined for application, and an in-vitro experiment result shows that the low-intensity magnetic field environment can remarkably improve the treatment effect of the chemotherapy drug. The new application of the weak magnetic field can be used for clinical adjuvant therapy of malignant tumors, the tumor inhibition effect of common chemotherapy drugs is improved, toxic and side effects are reduced, and a new reference basis is provided for clinical prevention and treatment of tumors.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biological medicine, and particularly relates to application of weak magnetic field combined with chemotherapy drugs in tumor treatment. BACKGROUND

[0002] Cancer has become one of the major public health problems worldwide, and its high incidence and mortality rate seriously endanger human health. According to the latest global cancer statistics report, there were nearly 200 million new cancer cases and 9.7 million cancer deaths worldwide in 2022. Among them, China, as a major cancer country, far exceeds other countries in the world in terms of both the number of new cases and the number of deaths, ranking first in the world.

[0003] Although traditional chemical drug therapy can effectively kill tumor cells and reduce tumor volume, it will also cause damage to normal cells, leading to a series of side effects such as nausea, vomiting, hair loss, bone marrow suppression, etc. With repeated use of chemotherapy drugs, tumors will also develop drug resistance, leading to tumor recurrence and metastasis. Therefore, how to improve the therapeutic effect of chemotherapy drugs has always been an important research direction in the field of oncology.

[0004] Magnetic field, as a kind of substance widely existing in nature, is one of the basic factors affecting the survival of living beings. More and more studies have shown that magnetic field can change biological functions such as cell proliferation, changes in cell membrane potential, cell ion transport, DNA expression, etc. In particular, magnetic fields with certain stable parameters can have a significant impact on tumor growth without affecting the growth of normal cells. Studies have found that the combination of appropriate intensity static magnetic field and chemotherapy drug doxorubicin can significantly improve the therapeutic effect of doxorubicin alone and prolong the survival time of breast cancer mice. In addition, the combination of static magnetic field and chemotherapy drugs such as paclitaxel, doxorubicin, cisplatin, and cyclophosphamide has a stronger effect on leukemia cells K562 than static magnetic field or chemotherapy drugs alone, and can induce cell cycle arrest.

[0005] In addition to the normal geomagnetic field, human beings may also be exposed to a weak magnetic field (HMF, static magnetic field with intensity less than 5 μT) environment, such as some artificially built special magnetic shielding places, or astronauts in long-term space flight, such as Mars magnetic field (<5 μT), lunar magnetic field (<300 nT). In recent years, a large number of scholars have found that exposure to a weak magnetic field can also inhibit the invasion and metastasis of tumor cells, resulting in fewer and smaller actin filaments of tumor cell pseudopods (11). These findings suggest that exposure to a weak magnetic field environment can be used as a method of tumor treatment, and a weak magnetic field environment is expected to solve the problem of tumor drug resistance. SUMMARY

[0006] The present application aims at the deficiencies in the prior art, and provides application of a weak magnetic field environment combined with chemotherapy drugs in tumor treatment.

[0007] To achieve the above object, the technical scheme adopted by the present application is as follows:

[0008] The combination of the weak magnetic field and the tumor chemotherapy drugs (including 5-fluorouracil, gemcitabine, doxorubicin, and paclitaxel) is used for experiments on melanoma cells, lung cancer cells, breast cancer cells, skin squamous cell carcinoma cells, and nasopharyngeal carcinoma cells, and the results show that the weak magnetic field has a synergistic effect on the chemotherapy drugs.

[0009] The weak magnetic field described in the present application is a static magnetic field, and the magnetic field strength is less than 20 nT.

[0010] The malignant tumor cell lines described in the present application include, but are not limited to, melanoma cells, lung cancer cells, breast cancer cells, nasopharyngeal carcinoma cells, liver cancer cells, esophageal cancer cells, skin squamous cell carcinoma cells, and colorectal cancer cells. Preferred tumors are melanoma cells B16F10, SK-MEL-5, lung cancer cells NCI-H460, breast cancer cells MCF-7, skin squamous cell carcinoma cells A431, and nasopharyngeal carcinoma cells KBC2.

[0011] The chemotherapy drugs described in the present application include, but are not limited to, alkylating agents such as cyclophosphamide, ifosfamide, and melphalan; antimetabolites such as methotrexate, fluorouracil, and gemcitabine; alkaloids such as paclitaxel, vinblastine, and vincristine; and antibiotics such as doxorubicin, bleomycin, and mitoxantrone. Preferred chemotherapy drugs are 5-fluorouracil, gemcitabine, doxorubicin, and paclitaxel.

[0012] The present application adopts the above technical scheme, and compared with the prior art, has the following technical effects: the weak magnetic field environment can significantly improve the therapeutic effect of the chemotherapy drugs, with the highest activity of the chemotherapy drugs being increased by 25.96 times and the maximum proliferation inhibition rate of the tumor cells being increased by 15.69%, thereby significantly improving the defects of multiple side effects and poor targeting in clinical chemotherapy.

[0013] In some embodiments of the present application, the HMF is also referred to as a weak magnetic field environment (hypomagnetic field, static magnetic field strength 0 < B ≤ 5 μT).

[0014] In some embodiments of the present application, the GMF is also referred to as a geomagnetic field environment (geomagnetic field, ~ 50 μT).

[0015] In some embodiments of the present application, the 5-FU is also referred to as 5-fluorouracil (5-Fluorouracil).

[0016] In some embodiments of the present application, the GE is also referred to as gemcitabine (Gemcitabine).

[0017] In some embodiments of the present application, the DOX is also known as Doxorubicin.

[0018] In some embodiments of the present application, the PTX is also known as Paclitaxel.

[0019] Beneficial effects:

[0020] 1. Significantly enhance the sensitivity of chemotherapy drugs

[0021] After the weak magnetic field (<20 nT) is combined with the chemotherapy drugs, the half maximal inhibitory concentration (IC50) of the chemotherapy drugs can be significantly reduced by more than 95% (such as the IC50 of PTX in skin squamous cell carcinoma A431 is reduced by 96.11%), indicating that the weak magnetic field can greatly improve the killing efficiency of the drugs on tumor cells and reduce the dosage of the chemotherapy drugs.

[0022] 2. Break through the bottleneck of tumor drug resistance

[0023] By inducing tumor cell cycle arrest (such as G2 / M phase arrest) and interfering with the DNA repair mechanism, the weak magnetic field can effectively delay or reverse the drug resistance of tumor cells to chemotherapy drugs (such as paclitaxel and doxorubicin), providing a new strategy for the treatment of clinically drug-resistant tumors.

[0024] 3. Reduce toxic side effects and improve treatment safety

[0025] The weak magnetic field itself has no significant toxicity to normal cells, and after being combined with the chemotherapy drugs, the dosage of the drugs can be reduced (such as the effective concentration of 5-FU under HMF is reduced to 1 / 4 of the conventional dosage), thereby reducing the side effects such as bone marrow suppression and gastrointestinal reactions, and improving the tolerance of patients.

[0026] 4. Broad-spectrum anti-tumor applicability

[0027] The synergistic therapeutic effect has been verified for melanoma (B16F10, SK-MEL-5), lung cancer (NCI-H460), breast cancer (MCF-7), skin squamous cell carcinoma (A431), nasopharyngeal carcinoma (KBC2), and other malignant tumors, covering the common high-incidence cancer types in clinical practice.

[0028] 5. Improve the maximum proliferation inhibition rate of tumor cells

[0029] Experimental data shows that the combination of the weak magnetic field and the chemotherapy drugs can improve the maximum proliferation inhibition rate of tumor cells by more than 15.69% (such as the inhibition rate of DOX in breast cancer MCF-7 is improved from 65% to 80%), which is significantly better than single chemotherapy or magnetic field alone.

[0030] 6. Provide a new paradigm for combination therapy

[0031] The weak magnetic field (<5 μT) is first proposed as a chemosensitizer, which breaks the limitation of traditional magnetic field treatment relying on high intensity (>1 T) or alternating magnetic field, and opens a new direction for physical-chemical combined treatment of tumors. BRIEF DESCRIPTION OF DRAWINGS

[0032] The application will be further described below in connection with the drawings and examples, in which:

[0033] Figure 1 It is a model (A) and a real object graph (B) of a weak magnetic cell incubator.

[0034] Figure 2 It is the effect of the weak magnetic field environment obtained in Example 2 combined with different concentrations of chemotherapeutic drugs (B16F10) on tumor cell activity for 72 h, the abscissa is the concentration of chemotherapeutic drugs (μg / mL), and the ordinate is the cell viability (%) A: 5-FU, B: GE, C: DOX, D: PTX.

[0035] Figure 3 It is the effect of the weak magnetic field environment obtained in Example 2 combined with different concentrations of chemotherapeutic drugs on tumor cell (SK-MEL-5) activity for 72 h, the abscissa is the concentration of chemotherapeutic drugs (μg / mL), and the ordinate is the cell viability (%) A: 5-FU, B: GE, C: DOX, D: PTX.

[0036] Figure 4 It is the effect of the weak magnetic field environment obtained in Example 3 combined with different concentrations of chemotherapeutic drugs on tumor cell (NCI-H460) activity for 72 h, the abscissa is the concentration of chemotherapeutic drugs (μg / mL), and the ordinate is the cell viability (%) A: 5-FU, B: GE, C: DOX, D: PTX.

[0037] Figure 5 It is the effect of the weak magnetic field environment obtained in Example 4 combined with different concentrations of chemotherapeutic drugs on tumor cell (MCF-7) activity for 72 h, the abscissa is the concentration of chemotherapeutic drugs (μg / mL), and the ordinate is the cell viability (%) A: 5-FU, B: GE, C: DOX, D: PTX.

[0038] Figure 6 It is the effect of the weak magnetic field environment obtained in Example 5 combined with different concentrations of chemotherapeutic drugs on tumor cell (A431) activity for 72 h, the abscissa is the concentration of chemotherapeutic drugs (μg / mL), and the ordinate is the cell viability (%) A: 5-FU, B: GE, C: DOX, D: PTX.

[0039] Figure 7 The effect of the weak magnetic field environment obtained in Example 6 combined with different concentrations of chemotherapy drugs for 72 hours on the activity of tumor cells (KBC2). The horizontal axis is the concentration of chemotherapy drugs (μg / mL), and the vertical axis is the cell viability (%). A: 5-FU, B: GE, C: DOX, D: PTX. Detailed Implementation

[0040] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments. However, the following embodiments are only for explaining the present invention, and the scope of protection of the present invention should include all the contents of the claims. Moreover, through the description of the following embodiments, those skilled in the art can fully implement all the contents of the claims of the present invention.

[0041] Example 1: Constructing a weak magnetic field environment

[0042] Cell culture magnetic shielding box (e.g.) Figure 1 The magnetic shielding box (as shown) consists of permalloy, a triaxial Helmholtz coil, and an aluminum layer magnetic shielding box. The permalloy and triaxial Helmholtz coil are primarily used for shielding static and low- to mid-frequency magnetic fields, while the aluminum layer is designed to shield high-frequency magnetic fields. The static magnetic field strength within the magnetic shielding box is below 20 nT. The residual magnetic field distribution within the magnetic shielding box is relatively uniform. The surface of the magnetic shielding box has sufficient pores to ensure adequate gas exchange for cells cultured within it. The magnetic shielding box is placed in a standard cell culture incubator to ensure cell culture at 37°C, 5% CO2, and 95% relative humidity. We also cultured control cells in a geomagnetic field environment on a stainless steel rack at the top of the magnetic shielding box in the same cell culture incubator (Thermo Scientific), where the local static magnetic field was approximately 50 μT.

[0043] Example 2: Effects of a weak magnetic field environment combined with chemotherapy drugs on the activity of melanoma cells

[0044] 1. Experimental Methods

[0045] Cell culture

[0046] Melanoma cell lines B16F10 and SK-MEL-5 were grown in DMEM high-glucose medium containing 10% fetal bovine serum (FBS), with 10X penicillin antibiotics added at a volume ratio of 1:100. The cells were then placed in an incubator at 37°C, 5% CO2, and saturated humidity. Cells in the logarithmic growth phase were used for experiments.

[0047] Cell plating

[0048] When the adherent cell density reaches 90%, trypsin is used to digest the cells. After an appropriate time, digestion is stopped with culture medium. The cells are centrifuged at 800 rpm for 5 min to remove the supernatant, resuspended in culture medium, counted, and then seeded into 96-well plates and incubated overnight at a density of 4000 cells / 180 μL of culture medium per well.

[0049] CCK8 assay for cell viability

[0050] Different concentrations of chemotherapeutic drugs (5-FU / GE / DOX / PTX) were incubated for 72 h under both geomagnetic field (GMF) and weak magnetic field (HMF) conditions. Then, 20 μL / well of CCK8 solution was added, and incubation was continued for 1.5 h. The absorbance (OD value) of each well was measured at 405 nm. Cell viability was calculated using the formula: Cell viability (%) = (OD value of drug-treated group - OD value of blank control group) / (OD value of control group - OD value of blank control group) × 100%. Results are expressed as the mean ± standard deviation of three independent experiments. The activity or toxicity of chemotherapeutic drugs is usually assessed using the half-maximal inhibitory concentration (IC50). 50 This is represented by ), calculated using GraphPad Prism6 software.

[0051] 2. Experimental Results

[0052] The results are as follows Figure 2 and Figure 3 As shown, a weak magnetic field synergistically inhibits melanoma cell activity in conjunction with chemotherapy drugs. 50 IC refers to the working concentration at which a drug inhibits 50% of cell proliferation. 50 The higher the value, the lower the cell-killing effect of the drug. As shown in Tables 1 and 2, compared with the GMF group, the IC50 values ​​of the chemotherapy drugs 5-FU, GE, DOX, and PTX in the HMF group against melanoma cells B16F10 and SK-MEL-5 were significantly lower. 50 All showed varying degrees of reduction, with the highest reduction reaching 92.27% (IC). 50GMF -IC 50HMF / IC 50GMF The results suggest that a weak magnetic field environment increases the sensitivity of drugs such as 5-FU, GE, DOX, and PTX.

[0053] In summary, this invention demonstrates that a weak magnetic field combined with chemotherapy drugs has a synergistic therapeutic effect on melanoma.

[0054] Table 1

[0055]

[0056] Table 2

[0057]

[0058] Example 3: Effect of weak magnetic field environment combined with chemotherapy drugs on lung cancer cell activity

[0059] 1. Experimental method

[0060] Cell culture

[0061] The lung cancer cell line NCI-H460 was grown in DMEM high glucose medium containing 10% fetal bovine serum (FBS), 10X double antibody was added at a volume ratio of 1:100, and placed in a incubator at 37°C, 5% CO2 and saturated humidity. The logarithmic growth phase cells were used for experiments.

[0062] Cell plating

[0063] When the density of the adherent cells reached 90%, trypsin was used to digest the cells. After a suitable time, the digestion was terminated with medium, and the supernatant was removed by centrifugation at 800 rpm / 5 min. The cells were resuspended in medium, counted, and then inoculated into 96-well plates at a density of 4000 cells / well / 180 μL medium and incubated overnight.

[0064] CCK8 method for determining cell viability

[0065] Different concentrations of chemotherapy drugs (5-FU / GE / DOX / PTX) were used to incubate lung cancer cells in the geomagnetic field (GMF) and weak magnetic field (HMF) for 72 h. Then 20 μL / well of CCK8 solution was added and incubated for 1.5 h. The absorbance (OD value) of each well was measured at 405 nm, and then the cell viability of the two groups was calculated. The formula was: cell viability (%) = (drug treatment group OD value-blank OD value) / (control group OD value-blank OD value) x 100%. The results were expressed as the mean ± standard deviation of three independent experiments. The activity or toxicity of the chemotherapy drugs was usually evaluated by the half maximal inhibitory concentration (IC 50 ) calculated by GraphPad Prism6 software.

[0066] 2. Experimental results

[0067] The results are shown in Figure 4 and Table 3. The weak magnetic field and chemotherapy drugs synergistically inhibited the activity of lung cancer cells. The IC 50 values of the drugs in inhibiting 50% of cell proliferation were calculated. The higher the IC 50 , the lower the killing power of the drug on the cells. As shown in Table 3, compared with the GMF group, the IC 50 of the chemotherapy drugs 5-FU, GE, DOX, and PTX on lung cancer cells NCI-H460 in the HMF group were reduced to different degrees, with the highest reduction of 95.87%, indicating that the weak magnetic field environment improved the drug sensitivity of 5-FU, GE, DOX, and PTX.

[0068] In conclusion, the present application proves that the weak magnetic field combined with chemotherapy drugs has a synergistic effect on the treatment of lung cancer.

[0069] Table 3

[0070]

[0071] Example 4: Effect of weak magnetic field environment combined with chemotherapy drugs on breast cancer cell activity

[0072] 1. Experimental method

[0073] Cell culture

[0074] The breast cancer cell line MCF-7 was grown in DMEM high glucose medium containing 10% fetal bovine serum (FBS), 10X double-antibodies were added at a volume ratio of 1:100, and placed in a 37°C, 5% CO2 and saturated humidity incubator, and logarithmic growth phase cells were used for experiments.

[0075] Cell plating

[0076] When the density of the adherent cells reached 90%, trypsin was used to digest the cells, and after a suitable time, the digestion was terminated with culture medium, centrifuged at 800 rpm / 5 min to remove the supernatant, and the cells were resuspended with culture medium, counted and then inoculated in 96-well plates for overnight incubation, with a density of 4000 cells / well / 180 μL of culture medium.

[0077] CCK8 method for determining cell viability

[0078] Different concentrations of chemotherapy drugs (5-FU / GE / DOX / PTX) were incubated in the geomagnetic field (GMF) and weak magnetic field (HMF) for 72 hours, then 20 μL / well of CCK8 solution was added, incubated for 1.5 hours, and the absorbance (OD value) of each well solution was measured at 405 nm, then the cell viability of the two groups was calculated, the calculation formula: cell viability (%) = (drug treatment group OD value-blank OD value) / (control group OD value-blank OD value) x 100%. The results are expressed as the mean ± standard deviation of three independent experiments. The activity or toxicity of the chemotherapy drugs is usually represented by the half maximal inhibitory concentration (IC 50 ) calculated by GraphPad Prism6 software.

[0079] 2. Experimental results

[0080] The results are shown in Figure 5 and Table 4, and the weak magnetic field and chemotherapy drugs synergistically inhibit breast cancer cell activity. IC 50 indicates the working concentration corresponding to the inhibition of 50% of cell proliferation. IC 50The higher, the lower the killing power of the cells after reflecting the effect of the drug. As shown in Table 4, compared with the GMF group, the IC 50 of 5-FU, GE, DOX and PTX on breast cancer cells MCF-7 in the HMF group was reduced by different degrees, with the highest reduction of 94.08%, indicating that the weak magnetic field environment improved the drug sensitivity of 5-FU, GE, DOX and PTX.

[0081] In summary, the present application proves that the weak magnetic field combined with the chemotherapeutic drug has a synergistic effect on the treatment of breast cancer.

[0082] Table 4

[0083]

[0084] Example 5: Effect of weak magnetic field environment combined with chemotherapeutic drug on skin squamous cell carcinoma cell activity

[0085] 1. Experimental method

[0086] Cell culture

[0087] The skin squamous cell carcinoma cell line A431 was grown in DMEM high-sugar medium containing 10% fetal bovine serum (FBS), 10X double-antibodies were added at a volume ratio of 1:100, and the culture was placed in a 37℃, 5% CO2 and saturated humidity incubator, and logarithmic growth phase cells were used for experiments.

[0088] Cell plating

[0089] When the density of the adherent cells reached 90%, trypsin was used to digest the cells, and after a suitable time, the digestion was terminated with culture medium, centrifuged at 800 rpm / 5 min to remove the supernatant, and the cells were resuspended with culture medium, counted and inoculated in 96-well plates for overnight incubation, with a density of 4000 cells / well / 180 μL culture medium.

[0090] CCK8 method for determining cell viability

[0091] Different concentrations of chemotherapeutic drugs (5-FU / GE / DOX / PTX) were used to incubate in the geomagnetic field (GMF) and weak magnetic field (HMF) for 72h, then 20 μL / well of CCK8 solution was added, incubated for 1.5h, and the absorbance (OD value) of each well solution was measured at 405nm, then the cell viability of the two groups was calculated, the calculation formula: cell viability (%)=(drug treatment group OD value-blank OD value) / (control group OD value-blank OD value) x 100%. The results are expressed as the mean ± standard deviation of three independent experiments. The activity or toxicity of the chemotherapeutic drug is usually represented by the half inhibitory concentration (IC 50 ), which is calculated by GraphPad Prism6 software.

[0092] 2. Experimental results

[0093] Results are shown in Table 5 and Table 5. Figure 6 As shown in Table 5 and Table 5, weak magnetic field and chemotherapy drugs synergistically inhibit the activity of skin squamous cell carcinoma cells. IC 50 The working concentration corresponding to the inhibition of 50% of cell proliferation. IC 50 The higher, the lower the killing power of the cells after the drug acts. As shown in Table 5, compared with the GMF group, the IC 50 of 5-FU, GE, DOX and PTX of the HMF group on skin squamous cell carcinoma cells A431 were reduced to different degrees, with the highest reduction of 96.11%, indicating that the weak magnetic field environment improved the drug sensitivity of 5-FU, GE, DOX and PTX.

[0094] In summary, the present application proves that weak magnetic field combined with chemotherapy drugs has a synergistic effect on the treatment of skin squamous cell carcinoma.

[0095] Table 5

[0096]

[0097] Example 6: Effect of weak magnetic field environment combined with chemotherapy drugs on the activity of nasopharyngeal carcinoma cells

[0098] 1. Experimental method

[0099] Cell culture

[0100] The nasopharyngeal carcinoma cell line KBC2 was grown in DMEM high-sugar medium containing 10% fetal bovine serum (FBS), 10X double-antibodies were added at a volume ratio of 1:100, and placed in a 37°C, 5% CO2 and saturated humidity incubator. The logarithmic growth phase cells were used for experiments.

[0101] Cell plating

[0102] When the density of the adherent cells reached 90%, trypsin was used to digest the cells, and after a suitable time, the digestion was terminated with culture medium, centrifuged at 800 rpm / 5 min to remove the supernatant, and the cells were resuspended with culture medium. After counting, the cells were inoculated in a 96-well plate and incubated overnight, with a density of 4000 cells per well / 180 μL of culture medium.

[0103] CCK8 method for determining cell viability

[0104] Different concentrations of chemotherapeutic drugs (5-FU / GE / DOX / PTX) were incubated for 72 h under both geomagnetic field (GMF) and weak magnetic field (HMF) conditions. Then, 20 μL / well of CCK8 solution was added, and incubation was continued for 1.5 h. The absorbance (OD value) of each well was measured at 405 nm. Cell viability was calculated using the formula: Cell viability (%) = (OD value of drug-treated group - OD value of blank control group) / (OD value of control group - OD value of blank control group) × 100%. Results are expressed as the mean ± standard deviation of three independent experiments. The activity or toxicity of chemotherapeutic drugs is usually assessed using the half-maximal inhibitory concentration (IC50). 50 This is represented by ), calculated using GraphPad Prism6 software.

[0105] 2. Experimental Results

[0106] The results are as follows Figure 7 As shown in Table 6, weak magnetic fields synergistically inhibit the activity of nasopharyngeal carcinoma cells with chemotherapy drugs. IC 50 IC refers to the working concentration at which a drug inhibits 50% of cell proliferation. 50 The higher the value, the lower the cell-killing effect of the drug. As shown in Table 6, compared with the GMF group, the IC50 of the chemotherapy drug on nasopharyngeal KBC2 cells in the HMF group was significantly lower. 50 The levels decreased to varying degrees, suggesting that the weak magnetic field environment improved the drug sensitivity to 5-FU, GE, DOX, and PTX.

[0107] In summary, this invention demonstrates that a weak magnetic field combined with chemotherapy drugs has a synergistic therapeutic effect on nasopharyngeal carcinoma.

[0108] Table 6

[0109]

[0110] The above description is merely a specific embodiment of this application, enabling those skilled in the art to understand or implement this application. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of this application. Therefore, this application is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features claimed herein.

Claims

1. The application of weak magnetic field combined with chemotherapy drugs in tumor treatment, characterized by: A weak magnetic field environment with a static magnetic field strength less than 20 nT is combined with a chemotherapeutic drug to act on tumor cells, so as to enhance the killing effect of the chemotherapeutic drug on tumor cells.

2. The application according to claim 1, characterized in that: The magnetic field strength of the weak magnetic field environment is 0 < B ≤ 5 μT, and it is a static magnetic field.

3. The application according to claim 1, characterized in that: The chemotherapeutic drug is selected from one or a combination of antimetabolic drugs, antibiotic drugs, and alkaloid drugs, and specifically includes 5-fluorouracil, gemcitabine, doxorubicin, and paclitaxel.

4. The application according to claim 3, characterized in that: The administration concentration of the chemotherapeutic drug is 0.01–100 μg / mL, and the combined exposure time with the weak magnetic field is 48–96 hours.

5. The application according to claim 1, characterized in that: The tumor is melanoma, lung cancer, breast cancer, cutaneous squamous cell carcinoma, or nasopharyngeal carcinoma, and the specific tumor cell lines include at least one of B16F10, SK-MEL-5, NCI-H460, MCF-7, A431, and KBC2.

6. The application according to claim 1, characterized in that: The weak magnetic field environment is realized by a magnetic shielding device, which includes a permalloy layer, a three-axis Helmholtz coil, and an aluminum layer magnetic shielding box. The residual magnetic field strength is lower than 20 nT, and it has a gas exchange channel to maintain cell culture conditions.

7. The application according to claim 1, characterized in that: The combined application reduces the half maximal inhibitory concentration of the chemotherapeutic drug by at least 85%, and increases the maximum proliferation inhibition rate of tumor cells by 10–25%.

8. The application according to claim 1, characterized in that: The weak magnetic field combined with the chemotherapeutic drug inhibits the proliferation of tumor cells in vitro or in vivo. Specifically, the cell viability is detected by the CCK-8 method, and the calculation formula is: cell survival rate (%) = (OD value of the drug treatment group - OD value of the blank) / (OD value of the control group - OD value of the blank) × 100%.

9. The application according to claim 1, characterized in that: The synergistic effect of the weak magnetic field and the chemotherapeutic drug is achieved by inducing tumor cell cycle arrest, and the toxicity to normal cells is significantly lower than that of using the chemotherapeutic drug alone.

10. The application according to claim 1, characterized in that: The treatment plan of the weak magnetic field combined with the chemotherapeutic drug is used for clinical adjuvant treatment to reduce the toxic and side effects of the chemotherapeutic drug and delay the generation of tumor drug resistance.

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