Application of combination of KN93 and doxorubicin in prevention and treatment of tumors and tumor metastasis induced by environmental pollutant PM2.5

Abstract

The invention discloses an application of combination of KN93 and doxorubicin in prevention and treatment of tumors and tumor metastasis induced by an environmental pollutant PM2.5. Experiments find that KN93 and doxorubicin are combined as active components for use, growth and proliferation of tumors induced by an environmental pollutant PM2.5 can be remarkably inhibited, the number of pulmonary metastasis nodules is remarkably reduced compared with that of a single drug group, and good synergistic anti-tumor and anti-metastasis effects are shown. Therefore, the KN93 and the doxorubicin can be combined to be used for developing the medicine for preventing or treating the PM2.5-induced tumor and tumor metastasis.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of medicine, and particularly relates to the application of KN93 and doxorubicin in combination in the prevention and treatment of tumor and tumor metastasis induced by environmental pollutants PM2.5. BACKGROUND

[0002] Fine particulate matter (PM2.5) refers to particulate matter with an aerodynamic diameter less than or equal to 2.5 microns, and is one of the main components of air pollution. In recent years, a large number of epidemiological and experimental studies have shown that PM2.5 exposure is not only closely related to respiratory and cardiovascular diseases, but also closely related to the occurrence and development process of tumors. It is worth noting that a large number of studies have shown that PM2.5 exposure significantly promotes the metastasis process of existing tumors. Studies have found that PM2.5 can activate systemic inflammatory response, induce oxidative stress, promote angiogenesis and increase vascular permeability, thereby creating favorable microenvironment conditions for tumor cell shedding, circulation, adhesion and colonization. The lung, as the main target organ and deposition site of PM2.5, is also the most common distant metastatic site of many malignant tumors, and PM2.5-induced tumor lung metastasis has become an important clinical problem in the current field of oncology.

[0003] At present, the treatment of tumor metastasis mainly relies on traditional cytotoxic chemotherapy drugs. Doxorubicin, as a classic anthracycline antitumor drug, exerts an antitumor effect through multiple mechanisms such as embedding DNA double strands, inhibiting topoisomerase II, and generating free radicals, and shows certain clinical efficacy in the treatment of various metastatic tumors. However, the existing chemotherapy treatment regimen has significant limitations: first, the overall remission rate of single chemotherapy drug for metastatic tumors is low, usually only 20-40%; second, chemotherapy drugs such as doxorubicin have obvious dose-limiting toxicity, especially cardiotoxicity, which seriously limits their clinical application; more importantly, there is currently a lack of specific treatment strategies for tumor metastasis induced by environmental pollutants (such as PM2.5) in clinical practice. Studies have shown that PM2.5 exposure may affect the sensitivity of tumor cells to traditional chemotherapy drugs by changing the tumor microenvironment and activating specific signaling pathways, further limiting the effectiveness of conventional chemotherapy regimens.

[0004] KN93 is a small molecule bioactive compound, and its molecular formula is C 26 H 29CIN2O4S, and the molecular weight is 501.04. Previous basic researches have shown that KN93 exhibits anti-tumor activity in various tumor models, especially in inhibiting tumor cell proliferation, inducing cell apoptosis, inhibiting tumor cell migration and invasion, and has good potential. However, the current researches mainly focus on the general anti-tumor effect of KN93, and there is no research to explore the specific effect of KN93 on tumor metastasis induced by environmental pollutants PM2.5. In addition, the key issues such as the effect of combination of KN93 with traditional chemotherapeutic drugs, whether it can produce synergistic effect, and whether it can reduce the toxic side effects of chemotherapeutic drugs, etc. have not been reported.

[0005] Developing effective therapeutic drugs and treatment regimens for PM2.5-induced tumor lung metastasis, exploring new combination therapy strategies that can enhance the effect of traditional chemotherapy while reducing the toxic side effects, not only has important scientific value, but also has urgent clinical application needs and broad social significance. SUMMARY

[0006] The purpose of the present application is to overcome the limitations of single chemotherapeutic drug treatment in the prior art, lack of specific treatment strategies for environmental pollutants-induced tumor growth, proliferation and metastasis, and provide the application of KN93 and doxorubicin in the preparation of drugs for preventing and treating environmental pollutants PM2.5-induced tumors and / or tumor metastasis.

[0007] The purpose of the present application is achieved by the following technical solutions: The application of KN93 and doxorubicin in the preparation of drugs for preventing and treating (preventing or treating) environmental pollutants PM2.5-induced tumors and / or tumor metastasis.

[0008] Further, the molecular formula of KN93 is C 26 H 29 CIN2O4S, and the molecular weight is 501.04.

[0009] Further, the drug for preventing and treating environmental pollutants PM2.5-induced tumors includes a drug for inhibiting the growth and / or proliferation of environmental pollutants PM2.5-induced tumors.

[0010] Further, the tumor is a malignant tumor; including breast cancer, etc.

[0011] Further, the tumor metastasis is preferably tumor lung metastasis; more preferably breast cancer lung metastasis.

[0012] Further, the dosages of KN93 and doxorubicin can be adjusted according to actual conditions; preferably, in an in vitro cell system, the dosage of KN93 is preferably 50 μM, and the dosage of doxorubicin is preferably 10 μM; in an in vivo animal experiment, the dosage of KN93 is 0.5 mg / kg, and the dosage of doxorubicin is 1 mg / kg.

[0013] Further, the mass ratio of KN93 to doxorubicin is 1:2.

[0014] Further, the drug is administered by tracheal instillation.

[0015] Further, the drug further comprises a pharmaceutically acceptable carrier or excipient, and is further prepared into a tracheal administration dosage form.

[0016] Further, the pharmaceutically acceptable carrier comprises physiological saline and the like.

[0017] A pharmaceutical composition for treating tumor growth, proliferation and / or tumor metastasis induced by environmental pollutants PM2.5, comprising an effective dose of KN93 and doxorubicin (as active ingredients).

[0018] Further, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier, such as physiological saline and the like.

[0019] Further, the mass ratio of KN93 to doxorubicin is 1:2.

[0020] The present application has the following advantages and effects relative to the prior art: The present application provides the use of KN93 combined with doxorubicin in treating PM2.5-induced tumor growth / proliferation and tumor lung metastasis, comprising an effective dose of KN93 and doxorubicin (as active ingredients), and the combination has the following advantages: ①High specificity: specifically targeting PM2.5-induced tumor lung metastasis, filling the gap in the treatment of environmental pollutant-related tumor metastasis, and providing a new treatment option for tumor patients in high-pollution environments; ②Significant synergistic effect: experimental results show that the combination of KN93 and doxorubicin shows significant synergistic anti-tumor effect in in vitro cell experiments and in vivo animal experiments, significantly better than using KN93 or doxorubicin alone; and experimental data show that the number of lung metastasis nodules in the combination group (KN93+doxorubicin) is significantly reduced (P<0.01) compared with the single-drug group; ③Good safety: the combination of KN93+doxorubicin does not significantly increase the side effects, and the body weight change in each group in the animal experiment has no significant difference, indicating that the combination scheme has good safety and tolerability while exerting strong therapeutic effect; 4. The administration regimen is optimized: the combined intermittent administration strategy ensures the synergistic effect of the drugs and reduces the risk of drug accumulation toxicity; the administration regimen is simple and easy to implement, the treatment cycle is reasonable, and the experimental data is reliable; 5. Wide clinical application prospect: the present application can provide a new solution for tumor metastasis treatment under the special environmental background of serious air pollution, especially PM2.5 pollution, and the combined therapy of KN93 and doxorubicin has good clinical value for PM2.5-induced tumor metastasis treatment. The technical scheme of the present application is scientific and reasonable, and provides a new treatment idea for tumor prevention and treatment in the field of environmental health (especially the treatment of environmental pollution-related tumor metastasis). BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1 Figure 4 is the in vitro cell experiment result of the influence of different drug treatments on cell viability (drug concentration: PM2.5: 50 μg / mL, KN93: 50 μM).

[0022] Figure 2 Figure 5 is a synergistic treatment effect diagram of KN93 combined with doxorubicin (drug concentration: PM2.5: 50 μg / mL, DOX: 10 μM, KN93: 50 μM).

[0023] Figure 3 Figure 6 is a flowchart of the animal experiment design of the present application.

[0024] Figure 4 Figure 7 is a graph of the body weight change of mice in each experimental group during drug administration (drug dosage: PM2.5: 1.25 mg / kg, DOX: 1 mg / kg, KN93: 0.5 mg / kg).

[0025] Figure 5 Figure 8 is a graph of the in vivo imaging detection results of the lung metastasis of mice in each experimental group on the 4th, 9th and 13th day after drug administration.

[0026] Figure 6 Figure 9 is a general observation image of the lung tissue of mice in each experimental group.

[0027] Figure 7 Figure 10 is a graph of the number of metastatic nodules in the lung of mice.

[0028] Figure 8 Figure 11 is a graph of the microscope observation results of the HE staining pathological sections of the lung tissue of mice in each experimental group (showing the pathological changes of the lung tissue and the tissue morphology of the metastatic nodules in each group). DETAILED DESCRIPTION

[0029] The application will be described in further detail below with reference to the embodiments. However, embodiments of the present application are not limited thereto. Unless otherwise specified, reagents, methods, and apparatuses used in the present application are those that are conventionally used in the art. Unless otherwise specified, the test methods in the following examples were conducted under conventional experimental conditions or under the conditions recommended by the manufacturer. Unless otherwise specified, the reagents and raw materials used in the present application are commercially available.

[0030] Example 1: In vitro cell experiment (1) Cell culture A 4T1 mouse breast cancer cell line (purchased from ATCC) was selected for in vitro experiments. The 4T1 cells were cultured in DMEM (Gibco) medium added with 10% (v / v) fetal bovine serum (FBS, Gibco) and 1% penicillin-streptomycin (Gibco). The culture conditions were 37°C, 5% CO2 incubator, and the cells were cultured to 90% confluence.

[0031] (2) Experiment 1: Verification of the inhibitory effect of KN93 on PM2.5-induced tumor cell proliferation Cell inoculation and grouping: The 4T1 cells were inoculated in a 96-well plate at 1×10 4 cells per well, and after 24 hours of culture, the cells were grouped and drug-treated. Three sets of parallel experiments were set up.

[0032] Experimental grouping: ① PM2.5 group: add PM2.5 50 μg / mL; ② KN93 group: add KN93 50 μM; ③ PM2.5+KN93 group: add PM2.5 50 μg / mL and KN93 50 μM; ④ Control group (Control): only add the same volume of culture medium.

[0033] (3) Experiment 2: Verification of the synergistic therapeutic effect of KN93 combined with doxorubicin Cell inoculation and grouping: The 4T1 cells were inoculated in a 96-well plate at 5×10³ cells per well, and after 24 hours of culture, the cells were grouped and drug-treated. Three sets of parallel experiments were set up.

[0034] Experimental grouping: ① PM2.5 group: add PM2.5 50 μg / mL; ② PM2.5+DOX group: add PM2.5 50 μg / mL, DOX 10 μM; ③ PM2.5 + KN93 group: PM2.5 50μg / mL and KN93 50μM were added; ④ PM2.5+DOX+KN93 group: PM2.5 50μg / mL, DOX 10μM and KN93 50μM were added; ⑤ Control group: Only an equal volume of culture medium was added.

[0035] (4) Reagent preparation PM2.5 particle preparation method: Small-diameter PM2.5 particles were prepared using NIST® SRM® 1649b standard particles (purchased from NIST). NIST® SRM® 1649b particles were suspended in ultrapure water and ultrasonically separated and dispersed. The particles were then centrifuged at 5000 rpm for 2 minutes, and the supernatant was collected to obtain the small-diameter particle fraction. The collected small-diameter particles were freeze-dried, weighed, and resuspended in ultrapure water (pH 6.7; Milli-Q, Bedford, MA) to the desired concentration for later use.

[0036] DOX (doxorubicin, also known as doxorubicin) and KN93 (purchased from MedChemExpress) were diluted to working concentrations in DMEM medium.

[0037] (5) Cell viability detection 4T1 cells were fed at a rate of 1×10 4 Cells were seeded at 1000 cells / well in 96-well plates and cultured overnight to allow adherence. The following day, cells were treated with PM2.5, doxorubicin (DOX, 5 μg / mL), or KN93 (75 μM) alone or in combination, and cultured for 24 hours. Cell viability was assessed using the MTT assay: 0.5 mg / mL MTT solution was added to each well, and the cells were incubated at 37°C for 4 hours. Then, 150 μL of dimethyl sulfoxide (DMSO) was added to dissolve the formazan crystals, and the absorbance was measured at 490 nm using a microplate reader. Relative cell viability was calculated for each treatment group with the absorbance of the control group as 100%.

[0038] In Experiment 1, the results were as follows: Figure 1As shown, the proliferation ability of 4T1 cells after PM2.5 treatment was significantly enhanced. Compared with the control group, PM2.5 increased the cell viability to about 160%, suggesting that PM2.5 can significantly promote the growth and expansion of breast cancer cells, and has a strong pro-tumor effect. Further, after the addition of small molecule inhibitor KN93, the PM2.5-induced proliferation was significantly reversed, and the cell viability of the PM2.5+KN93 group decreased to about 110%, basically close to the control level. This result shows that KN93 can effectively block the PM2.5-mediated proliferation signal, suggesting that the KN93-inhibited pathway may play a key role in PM2.5-induced tumor cell growth.

[0039] In experiment 2, as shown in Figure 2 , after the addition of the chemotherapeutic drug doxorubicin (PM2.5+DOX), the cell viability was further inhibited. Compared with single drug (PM2.5+KN93 group, cell viability 110%; PM2.5+DOX group, cell viability 130%), the double-drug combination group (PM2.5+DOX+KN93) after PM2.5 treatment showed the most significant inhibition effect, and the cell viability decreased to about 40%. This shows that the double-drug combination significantly enhances the anti-proliferation effect, showing obvious synergistic effect. This result shows that under the pressure of the tumor microenvironment caused by PM2.5, simultaneous inhibition of the CaMKII pathway and administration of a chemotherapeutic drug can maximally inhibit tumor cell growth, providing experimental evidence for a combination therapy strategy for pollution exposure-related tumor drug resistance or proliferation risk.

[0040] Example 2: Establishment of breast cancer lung metastasis animal model and drug treatment (1) Experimental animals Female BALB / c mice, weighing 18-20 g and 5-6 weeks old, were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. The animals were raised in a SPF-grade animal room with an environmental temperature of 22±2°C, a relative humidity of 45%-60%, and a 12h light-dark cycle. The animal experiment plan was approved by the Animal Ethics Committee of South China Institute of Technology, and the experimental operation complied with the relevant regulations on the use and management of experimental animals.

[0041] (2) Establishment of breast cancer lung metastasis model The 4T1-Luc2 cell line stably expressing luciferase (purchased from ATCC) was selected to establish a lung metastasis model. The cells were cultured in DMEM medium to the logarithmic growth phase, trypsinized and collected, washed with PBS 3 times, and then adjusted to a cell concentration of 5×10 6 The specific modeling process is shown in Figure 3 ​Preparation before experiment: 3 days before experiment (day "-3") and 1 day before experiment (day "-1"), the mice were pretreated, and the trachea was given nano PM2.5 (NanoPM2.5) treatment once, with a dose of 1.25 mg / kg each time; Experiment day 0: 5x10 5 The 4T1-Luc cells were injected into the tail vein of each mouse to induce tumor formation, and 4T1 tumor-bearing mice were obtained.

[0042] (3) Experimental grouping and treatment plan On day 4, the 4T1 tumor-bearing mice were randomly divided into 5 groups according to body weight, with 6-8 mice in each group: ① PBS control group: only given PBS treatment; ② PM2.5 exposure group: only PM2.5 exposure; ③ PM2.5+DOX group: PM2.5 exposure + doxorubicin treatment; ④ PM2.5+KN93 group: PM2.5 exposure + KN93 treatment; ⑤ PM2.5+DOX+KN93 group: PM2.5 exposure + combined treatment of KN93 and doxorubicin.

[0043] (4) PM2.5 preparation and administration PM2.5 preparation: SRM1648a standard particles were used to prepare small particle PM2.5 particles. The SRM1648a particles were suspended in ultrapure water, centrifuged at 5000 rpm for 2 minutes, and the small particle components in the supernatant were collected and freeze-dried, then prepared into working concentration with ultrapure water.

[0044] Administration method: after the mice were anesthetized with isoflurane, 1.25 mg / kg of PM2.5 solution was dropped into the trachea for exposure treatment.

[0045] (5) Drug treatment Drug administration: from day 4, intratracheal administration was performed once on days 4, 7, 10, and 13.

[0046] Dose: KN93 administration dose: 0.5 mg / kg; DOX administration dose: 1 mg / kg. KN93 and DOX were prepared with normal saline.

[0047] Intratracheal administration operation: after the mice were anesthetized, the trachea was exposed, and the drug solution was slowly injected into the trachea using a microsyringe to ensure uniform distribution in the lungs.

[0048] (6) Body weight change monitoring results To systematically evaluate the overall safety and tolerability of different treatment plans, the body weight of mice in each group was continuously monitored during the drug administration period. For example Figure 3and Figure 4 As shown, from day 2 to day 14 after administration, the body weight of mice in all experimental groups showed similar trends. Except for the PM2.5 treatment group, which showed a more significant decrease in body weight, no significant decrease or fluctuation was observed in the other treatment groups. Overall body weight remained stable within the range of approximately 23-26 g, with no significant difference compared to the control group. This result indicates that neither PM2.5+DOX, PM2.5+KN93, nor the combined treatment of PM2.5+DOX+KN93 caused significant systemic toxicity throughout the experiment, and the mice exhibited good tolerance to the administered drugs. The stability of body weight further supports the high safety of each treatment strategy at the experimental doses, providing a reliable experimental basis for subsequent efficacy analysis.

[0049] Example 3: In vivo imaging for detecting tumor metastasis The growth and metastasis of 4T1-Luc tumor cells in mice in Example 2 were dynamically monitored using in vivo bioluminescence imaging technology. Imaging was performed on days 4, 9, and 13 after drug administration to assess the tumor burden and metastasis in different treatment groups.

[0050] The results are as follows Figure 5 As shown: On day 4, all groups of mice exhibited weak luminescent signals confined to the chest and abdominal regions, with no significant differences between groups, indicating that the tumor burden was basically the same before grouping. By day 9, differences between groups gradually emerged: the tumor signal in the control group was slightly enhanced but still confined to the primary site; the luminescence intensity in the PM2.5 group was significantly increased and large-scale metastatic lesions appeared, with many mice showing strong red signals; the signal in the PM2.5+DOX group was significantly weaker than that in the PM2.5 group, but metastatic lesions were still present; the overall luminescence intensity in the PM2.5+KN93 group was significantly reduced, and the metastatic range was significantly reduced; while the PM2.5+KN93+DOX combination group showed the weakest tumor signal, with most mice showing only a weak blue area. By day 13, these differences had intensified further: the PM2.5 group showed a wider and stronger red luminescent area, indicating a significant increase in tumor metastasis; the tumor burden in the PM2.5+DOX group, although still high, was improved compared to the PM2.5 group; the luminescence signal in the PM2.5+KN93 group was significantly weakened, and the tumor burden was significantly reduced; the combined PM2.5+KN93+DOX group continued to show the best efficacy, with the lowest tumor signal, close to the control group level. Overall, the luminescence intensity from blue to red corresponded to an increasing trend in tumor burden from low to high. The results of this study indicate that PM2.5 exposure significantly promotes tumor growth and lung metastasis, while the combined intervention of KN93 and DOX can effectively counteract this pro-metastatic effect, exhibiting a significant synergistic anti-tumor effect superior to that of single drugs.

[0051] Example 4: Detection of lung metastatic nodules After the mice in the above experiment were sacrificed on day 13, their fresh lung tissues were taken out under sterile conditions and the surface bloodstains were washed thoroughly with PBS, followed by gross observation and quantitative analysis of lung metastases. The white metastatic nodules on the surface of the lung were carefully examined under a dissecting microscope, and the images were recorded using a digital camera; nodules with a diameter of ≥0.5 mm were counted. To improve the accuracy of counting, ImageJ software was used for auxiliary analysis, and the results were expressed as mean ± standard deviation, and the differences between groups were evaluated by t test, with a significant level of P < 0.05.

[0052] The results are shown in Figure 6 and Figure 7 : the statistical results show that there are significant differences in the number of lung metastatic nodules between different treatment groups (P < 0.01): the average number of nodules in the control group is about 18, and it increases significantly to about 60 after PM2.5 exposure; the number of nodules in the PM2.5+DOX group decreases to about 38, suggesting that DOX can partially inhibit PM2.5-induced tumor metastasis; the number of metastatic nodules in the PM2.5+KN93 group further decreases to about 20, while the PM2.5+KN93+DOX combined treatment group shows the most prominent effect, with only about 10 nodules, and the inhibitory effect is the most significant. The overall results show that PM2.5 exposure significantly promotes the lung metastasis of 4T1 tumors, and the combined intervention of KN93 and DOX can effectively reverse this pro-metastatic effect, and the combination of KN93 and DOX has a significantly better effect than single drug treatment, showing strong synergistic anti-metastatic potential.

[0053] Example 5: Histopathological examination After the above isolated lung tissues were fixed in 4% paraformaldehyde for 24 hours, they were washed with running water and dehydrated with 70% to 100% gradient alcohol, xylene transparent and paraffin embedding, then the paraffin blocks were cut into 4 μm thick sections and attached to glass slides, and baked at 60°C for 2 hours to ensure that the sections were fully stretched and firmly attached. The prepared sections were further subjected to HE staining, including xylene dewaxing, gradient alcohol hydration, hematoxylin staining, 1% hydrochloric acid alcohol differentiation, eosin re-staining, and gradient alcohol dehydration, xylene transparency and neutral gum sealing. Finally, the morphological changes of the lung tissues were observed under a light microscope, focusing on the cell morphology, arrangement characteristics and boundary with normal lung tissue of the metastatic nodules in each group of mice, and representative fields were photographed.

[0054] The results are shown in Figure 8As shown: The results show that the lung tissue structure of the control group is complete, the alveolar wall is thin and clear, and no tumor cell infiltration is observed; the PM2.5 exposure group shows obvious tissue damage, including alveolar wall thickening, inflammatory cell infiltration and local structure destruction, indicating that PM2.5 significantly aggravates the pathological changes of lung tissue; the tissue damage of the PM2.5+DOX group is alleviated, but scattered tumor cell foci and inflammatory reactions can still be seen; the lung tissue structure of the PM2.5+KN93 group is significantly improved, and the tumor cell infiltration and inflammation are significantly reduced; and the PM2.5+KN93+DOX combined treatment group shows the best effect, the lung tissue structure is almost restored to normal state, the tumor cell infiltration is the least, and the inflammatory reaction is the lightest, showing strong synergistic anti-tumor and anti-metastasis effect. Therefore, the combined treatment of KN93 and DOX can protect the alveolar structure to the greatest extent and effectively reduce the tumor burden, indicating that this strategy has the most significant therapeutic advantage in inhibiting PM2.5-induced lung metastasis of breast cancer.

[0055] In summary, the present application first discloses the significant protective effect of KN93 in the process of PM2.5-induced tumor metastasis, and innovatively proposes a combined treatment strategy of KN93 and DOX, successfully constructing a new prevention and treatment system for PM2.5-driven tumor metastasis. The experimental results clearly show that the combined therapy can exert a strong synergistic anti-tumor effect, effectively inhibiting tumor growth and metastasis, providing a new solution to the major public health challenge of environmental pollution-related tumor progression, and showing good clinical application prospect and industrialization potential in the fields of environmental health and tumor prevention and treatment.

[0056] The technical route and core idea of the present application can also provide inspiration for related research, and those skilled in the art can further explore drug combinations with similar mechanisms of action on this basis, and adjust and optimize the drug dosage, administration method and treatment cycle, etc. without departing from the basic concept of the present application, so as to expand its application range and improve the actual treatment effect.

[0057] Therefore, the above embodiments are the preferred embodiments of the present application, and the embodiments of the present application are not limited by the above embodiments, and any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present application should be equivalent replacement methods, all of which are included in the protection scope of the present application.

Claims

1. Use of KN93 and doxorubicin in combination in the preparation of a medicament for preventing and treating tumor and / or tumor metastasis induced by environmental pollutants PM2.

5.

2. The use according to claim 1, wherein: the tumor is a malignant tumor; and the tumor metastasis is tumor lung metastasis.

3. The use according to claim 2, wherein: the tumor is breast cancer; and the tumor metastasis is breast cancer lung metastasis. The mass ratio of KN93 to doxorubicin is 1:

2. The medicament is administered by tracheal instillation. The medicament further comprises a pharmaceutically acceptable carrier or excipient. The pharmaceutically acceptable carrier is physiological saline.

4. Use according to claim 1, characterized in that: An effective dose of KN93 and doxorubicin is contained.

5. The use according to claim 1, characterized in that: The tumor is a malignant tumor.

6. Use according to claim 1, characterized in that: The tumor metastasis is tumor lung metastasis.

7. Use according to claim 6, characterized in that: The mass ratio of KN93 to doxorubicin is 1:

2.

8. A pharmaceutical composition for treating tumor growth, proliferation and / or tumor metastasis induced by environmental pollutant PM2.5, characterized in that:

10. The pharmaceutical composition according to claim 8, wherein: the tumor is breast cancer; and the tumor metastasis is breast cancer lung metastasis. ​ ​ 9. The pharmaceutical composition of claim 8, wherein: ​ ​ ​ ​

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