Application of dauricine in preparation of medicine for treating non-small cell lung cancer

Abstract

The invention discloses application of dauricine in preparation of a medicine for treating non-small cell lung cancer, belongs to medical application of the dauricine in the technical field of biological medicines, and creatively discovers that the dauricine has an excellent effect of treating the non-small cell lung cancer. The proliferation of non-small cell lung cancer cells can be inhibited by reducing mitochondrial membrane potential, inhibiting Notch3 protein activity, reducing the expression level of DLL4 protein and the like; meanwhile, a good treatment effect is shown in a non-small cell lung cancer mouse model, growth and proliferation of non-small cell lung cancer cells can be remarkably inhibited, apoptosis of the non-small cell lung cancer cells is induced, depolarization of mitochondria of the non-small cell lung cancer cells is induced, Notch3 protein activity is remarkably inhibited, expression of DLL4 protein is reduced, and the anti-cancer effect is achieved. The invention provides a new path for the application of the dauricine in treating the non-small cell lung cancer, and provides a new thought and strategy for the development and utilization of the dauricine.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology and relates to the medicinal use of dauricine, and in particular to the use of dauricine in the preparation of a drug for treating non-small cell lung cancer. Background Art

[0002] Lung cancer is one of the most common cancers, accounting for about 19% of all cancer deaths worldwide. Among the total incidence of lung cancer, non-small cell lung cancer accounts for the highest proportion, accounting for about 85%. Currently, chemotherapy combined with surgery and radiotherapy has been used to treat lung cancer, but its side effects, such as nephrotoxicity and neurotoxicity, are detrimental to the survival of patients. Therefore, there is an urgent need to develop treatment strategies with less toxic side effects.

[0003] Natural products are an important source of anti-tumor drugs. Dauricine (MenispermumdauricumDC.), also known as northern bean root, is a traditional Chinese medicine in my country. It was first recorded in the "Chinese Medicinal Plants" and is mainly produced in Northeast China, North China, Shaanxi and other places. Northern bean root is bitter and cold in nature, slightly toxic, and enters the lung, stomach, and large intestine meridians. It has the effects of clearing away heat and detoxifying, dispelling wind and relieving pain. Dauricine (molecular formula C 38 H 44 N2O6) is one of the various alkaloids extracted and separated from the vines of the root of the northern bean root. It is classified as a dibenzyltetrahydroisoquinoline alkaloid connected by a tail-tail single oxygen bridge in terms of chemical structure. Dauricine has high fat solubility and can easily pass through the blood-brain barrier. Dauricine is often used in anti-inflammatory and anti-arrhythmic treatments. In clinical practice, dauricine and its active substances are mainly used for sore throat, enteritis, dysentery, rheumatic paralysis and other diseases.

[0004] The invention patent application with application number 202311796163.0 discloses the use of dauricine in the preparation of drugs for preventing or treating non-small cell lung cancer. It creatively discovered that dauricine has excellent effects in preventing and treating non-small cell lung cancer. It can inhibit the proliferation of non-small cell lung cancer cells by increasing the level of ROS in non-small cell lung cancer cells and downregulating the levels of GPX4 and SLC7A11. At the same time, it shows good preventive and therapeutic effects in non-small cell lung cancer mouse models, and can significantly reduce the volume of mouse tumors. In addition, it also creatively combines dauricine with osimertinib or its pharmaceutically acceptable salt as a drug for preventing or treating non-small cell lung cancer, which can not only increase the sensitivity of non-small cell lung cancer to osimertinib, reduce the dosage of osimertinib, and improve the safety of medication, but also has a more significant effect of inhibiting non-small cell lung cancer than the use of osimertinib or dauricine alone, achieving a synergistic promotion effect.

[0005] However, in the prior art, there is no report that dauricine has the ability to inhibit the proliferation of non-small cell lung cancer by reducing mitochondrial membrane potential, inhibiting the activity of Notch3 protein or reducing the expression level of DLL4 protein, thereby playing an anti-lung cancer role. Summary of the invention

[0006] The purpose of the present invention is to provide an application of dauricine in the preparation of a drug for treating non-small cell lung cancer, creatively inhibiting the proliferation of non-small cell lung cancer by reducing mitochondrial membrane potential, inhibiting the activity of Notch3 protein or reducing the expression level of DLL4 protein through dauricine, thereby achieving the treatment of non-small cell lung cancer.

[0007] In order to achieve the above-mentioned purpose, the present invention specifically adopts the following technical solutions: The application of dauricine in the preparation of drugs for treating non-small cell lung cancer. Dauricine inhibits the proliferation of non-small cell lung cancer cells by reducing mitochondrial membrane potential, inhibiting Notch3 protein activity, or / and reducing the expression level of DLL4 protein.

[0008] Furthermore, dauricine inhibits the proliferation of non-small cell lung cancer cells by reducing mitochondrial membrane potential and inducing tumor cell apoptosis.

[0009] Furthermore, dauricine inhibits the proliferation of non-small cell lung cancer cells by reducing mitochondrial membrane potential and inducing tumor cell necrosis.

[0010] The beneficial effects of the present invention are as follows: In the present invention, it is creatively discovered that dauricine has an excellent effect in preventing and treating non-small cell lung cancer. It can inhibit the proliferation of non-small cell lung cancer cells by reducing mitochondrial membrane potential, inhibiting the activity of Notch3 protein, reducing the expression level of DLL4 protein, etc.; at the same time, it shows a good preventive and therapeutic effect in a non-small cell lung cancer mouse model, and can significantly inhibit the growth and proliferation of non-small cell lung cancer cells, induce apoptosis of non-small cell lung cancer cells, induce mitochondrial depolarization of non-small cell lung cancer cells, and significantly inhibit the activity of Notch3 protein, reduce the expression of DLL4 protein, and play an anti-cancer effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 This is a schematic diagram of the effect of different concentrations of dauricine on the proliferation of A549 and H1299 cells (Note: * P <0.05,** P <0.01 vs. 0 μM); Figure 2 EC in the present invention 50 and CC 50 Fitting curve graph; Among them, the above picture shows the EC of A549 50 Fitting curve graph, the middle graph is the EC of H1299 50 Fitting curve diagram, the figure below is the CC of BEAS-2B 50 Fitting curve graph; Figure 3 It is the flow cytometric graph of the effect of dauricine on apoptosis of A549 cells; Figure 4 It is the flow cytometric graph of the effect of dauricine on apoptosis of H1299 cells; Figure 5 This is a schematic diagram of the effect of dauricine on the apoptosis rate of A549 and H1299 cells (Note: * P <0.05,** P <0.01 vs. 0 μM); Figure 6 This is the flow cytometric diagram of the effect of dauricine on mitochondrial membrane potential of A549 cells (Note: * P <0.05,** P <0.01 vs. 0 μM); Figure 7 It is the flow cytometric graph of the effect of dauricine on mitochondrial membrane potential of H1299 cells; Figure 8 This is a schematic diagram of the effect of dauricine on mitochondrial membrane potential of A549 and H1299 cells (Note: * P <0.05,** P <0.01 vs. 0 μM); Fig. 9 This is a schematic diagram of the establishment of Lewis lung cancer ectopic mouse model and drug intervention; Fig.10 This is a schematic diagram of the changes in tumor volume in each group of mice (Note: ## P <0.01vs.model); Fig.11 This is a schematic diagram of the changes in tumor weight of mice in each group (Note: # P <0.05,## P <0.01vs.model); Fig.12 is a schematic diagram of the tumor photos of mice in each group; Fig.13 is a schematic diagram of the tumor tissue morphology of mice in each group (HE staining, ×200); Fig.14 This is a schematic diagram of the pathological section scores of each group of mice (Note: # P <0.05,## P <0.01vs.model); Fig.15This is a schematic diagram of the effect of dauricine on Notch3 protein expression in A549 and H1299 cells (Note: * P <0.05,** P <0.01 vs. 0 μM); Fig.16 This is a schematic diagram of the effect of dauricine on Notch3 protein expression in A549 and H1299 cells (Note: * P <0.05,** P <0.01 vs. 0 μM); Fig.17 This is a schematic diagram of the effect of batroxine on the expression of DLL4 protein in A549 and H1299 cells (Note: * P <0.05,** P <0.01 vs. 0 μM); Fig.18 This is a schematic diagram of the effect of batroxine on the expression of DLL4 protein in A549 and H1299 cells (Note: * P <0.05,** P <0.01 vs. 0 μM); Fig.19 This is a schematic diagram of the effect of dauricine on the expression of Notch3 and DLL4 proteins in tumor tissues of Lewis lung cancer mice (Note: * P <0.05vs.0mg / kg). DETAILED DESCRIPTION

[0012] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all of the embodiments.

[0013] Therefore, based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative work shall fall within the scope of protection of the present invention.

[0014] The use of dauricine in the preparation of a drug for treating non-small cell lung cancer is characterized in that dauricine inhibits the proliferation of non-small cell lung cancer cells by reducing mitochondrial membrane potential, inhibiting Notch3 protein activity, or / and reducing the expression level of DLL4 protein.

[0015] In particular, dauricine inhibits the proliferation of non-small cell lung cancer cells by reducing mitochondrial membrane potential and inducing tumor cell apoptosis.

[0016] In particular, dauricine inhibits the proliferation of non-small cell lung cancer cells by reducing mitochondrial membrane potential and inducing tumor cell necrosis.

[0017] Baticine can inhibit the proliferation of non-small cell lung cancer by inducing tumor cell apoptosis, reducing mitochondrial membrane potential, promoting tumor cell necrosis, inhibiting the activity of Notch3 protein, and reducing the expression level of DLL4 protein, thereby playing an anti-lung cancer role.

[0018] The application of dauricine provided by the present invention in the preparation of drugs for treating non-small cell lung cancer is described in detail below in conjunction with the examples, but they should not be construed as limiting the scope of protection of the present invention.

[0019] The animals, cells, reagents and instruments used in the following examples are: 1. Animals and cells Thirty-six SPF C57BL / 6 female mice aged 4 to 5 weeks, weighing 14 to 16 g, were provided by Beijing Weitonglihua (Beijing) Biotechnology Co., Ltd., with animal production license number SCXK (Beijing) 2021-0006. They were kept in the SPF animal room of the Antiviral Collaborative Innovation Center of Shandong University of Traditional Chinese Medicine, with a temperature of (25±1)℃, a humidity of (55±5)%, and a 12-h light-dark cycle. The following test examples were approved by the Animal Experiment Ethics Committee of Shandong University of Traditional Chinese Medicine.

[0020] Mouse Lewis lung cancer cell lines, human non-small cell lung cancer cells (A549, H1299), and human normal lung epithelial cells (BEAS-2B) were purchased from Wuhan Pronocell Life Science Technology Co., Ltd.

[0021] 2. Reagents and instruments Dauricine (lot number: 23022803, Chengdu Pufeide Biotechnology Co., Ltd.); Notch3 antibody (lot number: 55114-1-AP) and DLL4 antibody (lot number: 0106510201) were purchased from Wuhan Sanying Biotechnology Co., Ltd.; AnnexinV / 7-AAD apoptosis kit (lot number: E-CK-A212, Wuhan Elerite Biotechnology Co., Ltd.); JC-1 kit (lot number: C2003S, Shanghai Bio-Technology Co., Ltd.); Matrigel (lot number: 20220422c, Shanghai Nova Pharmaceutical Technology Co., Ltd.); PEG 300 (lot number: 230284, MCE); Tween 80 (lot number: 120357, MCE); DMSO (lot number: 3231026003, Beijing Solebow Technology Co., Ltd.); biological microscope (BX53, OLYMPUS); multifunctional real-time label-free cell analyzer (XCElligence RTCA DP, Aisen Biotechnology); flow cytometer (C6, BD).

[0022] Example 1. Effect of dauricine on proliferation of A549 and H1299 cells This embodiment uses the RTCA method to detect cell proliferation activity. Real-time label-free cell analysis (RTCA) technology is a real-time cell monitoring technology based on microelectronic impedance technology, with cell index (CI) as the evaluation index. The size of the CI value depends on the size, shape, number and adhesion of the cells. This technology does not require markers and can realize real-time dynamic observation of cell growth changes for several consecutive days. The cell detection plate is an E-plate 16-well platinum electrode plate.

[0023] The specific steps of this experiment are: Step 1. Add 50 µL of growth medium to 16 wells of the cell assay plate.

[0024] Step 2: Place the cell assay plate on the RTCA workstation.

[0025] Step 3. Click the Scan Plate option in the RTCA system. The RTCA system will automatically scan and check whether the contact is good on the "Message" page. If it displays "Connection OK", it means the contact is good.

[0026] Step 4: Start measuring the baseline to ensure that the selected cell wells are in normal contact and the CI values ​​of all wells are lower than 0.063.

[0027] Step 5. Take out the cell detection plate and plate the cells. Each well contains 5000 A549, H1299, and BEAS-2B cells / 100µL, respectively.

[0028] Step 6: Place the cell detection plate in a clean bench at room temperature for 30 minutes.

[0029] Step 7. Place the cell assay plate back onto the RTCA workstation in the incubator.

[0030] Step 8. After clicking the "Scan Plate" option, the RTCA system automatically scans and starts Step 2. When the cells enter the plateau phase, Step 2 is terminated and the cell detection plate is removed from the RTCA Station.

[0031] Step 9: Discard the culture medium and add 100 µL of a series of dauricine concentration gradients to the cells. Set up a normal control group, and the dauricine concentration gradients in each normal control group are: 200, 100, 50, 25, 12.5, 6.25, 0 μM.

[0032] Step 10. Place the cell detection plate back on the RTCA Station, click the "Scan Plate" option, and start Step 3.

[0033] Step 11: After 72 hours of dauricine intervention, calculate the half effective inhibitory concentration (CC) of A549 and H1299 cells. 50 , EC50 of cytotoxic concentration for BEAS-2B cells 50 , C.C. 50 and EC 50 The calculation formula is: .

[0034] Table 1 RTCA system procedures

[0035] Test results: The experimental results of dauricine on the proliferation of A549 and H1299 cells are as follows Figure 1 As shown in the figure, compared with the 0μM group, batricine from low to high dose groups had a significant inhibitory effect on the proliferation of A549 and H1299 cells. As the concentration of batricine increased, the inhibitory effect on cell proliferation became greater, forming a concentration-dependent relationship, and the difference was statistically significant (P<0.01).

[0036] After 72 h of dauricine intervention, the half effective inhibitory concentration (EC) of A549 and H1299 cells was calculated. 50 ), the half cytotoxic concentration (CC 50 ), the calculation results are as follows Figure 2 As shown. After calculation and fitting, EC 50A549 =18.1μM; EC 50H1299 =11.3μM; CC 50BEAS-2B =45.9μM, the therapeutic index TI values ​​are: TI A549 =2.54,TI H1299 =4.06, indicating that dauricine has the effect of inhibiting the growth and proliferation of non-small cell lung cancer and has a high safety.

[0037] Example 2: Effect of dauricine on apoptosis of A549 and H1299 cells The specific steps of this experiment are: Step 1: The A549, H1299, and BEAS-2B cells (human non-small cell lung cancer cells (A549, H1299) and human normal lung epithelial cells (BEAS-2B) purchased from Wuhan Pronocell Life Science Co., Ltd., i.e., the cells for subculture) were cultured at 2*10 5 The cells were seeded in 6-well plates and cultured overnight.

[0038] Step 2, set up a normal control group, and treat with dauricine for 48 hours, wherein the concentration gradients of dauricine in each normal control group are: 30, 20, 10, 0 μM.

[0039] Step 3: Digest the cells treated with dauricine in each group with EDTA-free trypsin.

[0040] Step 4: Centrifuge the cells in each group at 1000 r / min for 5 min, collect the cells, and then wash them twice with pre-cooled PBS solution.

[0041] Step 5. Add 500 μL of Binding Buffer to each group of cells and resuspend them to adjust the cell concentration to 1.5×10 5 / mL, and double staining was performed (the specific steps were carried out according to the instructions of the Annexin V FITC / 7-AAD Cell Apoptosis Detection Kit).

[0042] Step 6: After staining, the apoptosis rate of cells in each group was detected by flow cytometry within 1 hour.

[0043] Test results: The apoptosis of A549 and H1299 cells was detected by flow cytometry with different concentrations of dauricine. Figure 3 , Figure 4 , Figure 5 As shown in the figure, compared with the 0 μM group, with the increase of dauricine concentration, the apoptosis rate of cells in each group increased significantly (P<0.05). It can be seen that dauricine can induce cell apoptosis in a concentration-dependent manner.

[0044] Example 3: Effect of dauricine on mitochondrial membrane potential of A549 and H1299 cells In this embodiment, flow cytometry is used to detect the mitochondrial membrane potential of cells.

[0045] The specific steps of this experiment are: Step 1. Inoculate the cultured A549, H1299, and BEAS-2B cells (human non-small cell lung cancer cells (A549, H1299) and human normal lung epithelial cells (BEAS-2B) purchased from Wuhan Pronocell Life Science Co., Ltd., i.e., cultured cells) in a 6-well plate at a number of 2*105 cells / well and cultured overnight.

[0046] Step 2, set up a normal control group, and treat with dauricine for 48 hours, wherein the concentration gradients of dauricine in each normal control group are: 30, 20, 10, 0 μM.

[0047] Step 3: Digest the cells treated with dauricine in each group with EDTA-free trypsin.

[0048] Step 4: Centrifuge the cells in each group at 1000 r / min for 5 min, collect the cells, and then wash them twice with pre-cooled PBS solution.

[0049] Step 5. Add JC-1 (final concentration 2 μM) in dark place, incubate at 37°C for 20 min, centrifuge and discard the supernatant, then wash and mix the cells with PBS.

[0050] Step 6, using flow cytometry to detect cell mitochondrial membrane potential.

[0051] Test results: Flow cytometry was used to detect the mitochondrial membrane potential of A549 and H1299 cells treated with different concentrations of dauricine. Figure 6 , Figure 7 , Figure 8 As shown in the figure, compared with the 0 μM group, with the increase of dauricine concentration, the mitochondrial membrane potential decreased significantly (*P<0.05, **P<0.01). It can be seen that dauricine can induce mitochondrial depolarization in a concentration-dependent manner.

[0052] Example 4: Effect of dauricine on tumor growth in Lewis lung cancer mice Before exploring the effect of dauricine on the growth of Lewis lung cancer mice, it is necessary to establish a Lewis lung cancer ectopic mouse model, specifically: Preparation of Lewis lung cancer cell suspension: Lewis lung cancer cells were placed in DMEM culture medium (containing 10% FBS, 1% P / S) and incubated in an incubator at 37°C and 5% CO2 concentration. After the cell confluence rate reached 70%-80%, they were digested with trypsin, centrifuged and the supernatant was discarded, washed with PBS, and the live cells were counted and the live cell rate was greater than 95%. They were resuspended in PBS and the cell suspension concentration was adjusted to 1×10 7 Pieces / mL.

[0053] Animal grouping and treatment: 36 female, 4-6 weeks old, C57BL / 6 mice were adaptively raised for 3 days. The hair on the right axilla of the mice was removed to expose the skin, and the mice were anesthetized with isoflurane breathing. The right axilla of the mice was disinfected with 75% ethanol, and the needle was inserted obliquely into the right axilla, and 0.1 mL of Lewis lung cancer cell solution (model group mice, 30 mice) or serum-free DMEM medium (blank group mice, 6 mice) was injected subcutaneously. The skin surface of the mice was observed, and after a mung bean-sized skin mound was formed, the syringe was rotated to remove the needle.

[0054] Animal grouping and intervention: 30 model group mice were randomly divided into tumor group, high-dose dauricine group (15 mg / kg / day), medium-dose group (10 mg / kg / day), low-dose group (5 mg / kg / day), and cisplatin group (3 mg / kg / 2 days), with 6 mice in each group. The drug was administered on the third day after modeling, and the administration was intraperitoneal injection for a period of 14 days. The blank group and tumor group mice were intraperitoneally injected with an equal volume of normal saline. The dauricine solvent was prepared by adding 10% DMSO, 40% PEG300, 5% Tween80, and 45% normal saline in sequence (the percentage refers to the volume proportion of the solvent in the final solution), and it was prepared as needed.

[0055] Establishment of Lewis lung cancer ectopic mouse model and drug intervention, such as Fig. 9 shown.

[0056] 1. Determination of tumor inhibition rate The growth of transplanted tumors was observed daily. The volume of transplanted tumor = (long diameter × short diameter) 2 ) / 2, and the tumor growth curve was drawn. 24 hours after the last administration, the mice were anesthetized with isoflurane, and the tumor tissues were aseptically removed, weighed, and photographed.

[0057] Test results: The changes of tumor volume and weight of mice in each group were as follows: Fig.10 , 11 As shown. Compared with the tumor group, the tumors in the medium-dose and high-dose groups of dauricine grew slowly and their volumes were significantly reduced (##P<0.01). After dissection, the tumor tissues of the mice were weighed. Compared with the model group, the tumor weights in the medium-dose and high-dose groups of dauricine were significantly reduced (#P<0.05, ##P<0.01), and the tumors in the low-dose group of dauricine were reduced but there was no significant difference.

[0058] 2. Histopathological examination At room temperature, the tumor tissue was fixed with 4% paraformaldehyde, then embedded in paraffin blocks and cut into 5 μm sections for staining, dewaxed, and stained with hematoxylin-eosin staining. After dehydration and sealing, the morphological changes of the tumor tissue were observed under a light microscope at a magnification of × 200. The pathological scores of mice in each group were calculated according to Table 1.

[0059] Table 2 Pathological scoring criteria for mouse tumor tissue

[0060] Test results: HE staining results showed that Fig.13As shown, the tumor tissue cells of the model group mice were closely arranged, with clear boundaries, darkly stained nuclei, and no necrotic areas were observed; the tumor tissue cells of the cisplatin group and the dauricine intervention group were loosely arranged, with blurred boundaries, necrosis, and a significantly increased necrotic area.

[0061] Pathological section scores of mice in each group were as follows: Fig.14 As shown, the pathological section scores of mice in the model group were the highest; the pathological section scores of mice in the low-dose baticine group were second; the pathological section scores of mice in the high-dose baticine group and the medium-dose baticine group were not much different; and the pathological section scores of mice in the cisplatin group were the lowest.

[0062] (III) Immunoblotting experiment (with Notch3 and DLL4) The tumor tissue was minced, homogenized with lysis buffer, and placed in an ice bath for 15 minutes. The supernatant was collected after centrifugation, and the protein concentration was determined by the BCA method. The reduced protein loading buffer was added for metal bath denaturation for 15 minutes. The loading amount was 40 μg of total protein, which was separated by 7.5% sodium dodecyl sulfate polyacrylamide gel electrophoresis and then transferred to a 0.45 μm PVDF membrane. After blocking with 5% BSA for 2 hours at room temperature, the PVDF membrane was incubated with primary antibodies: Notch3 (1:1000), DLL4 (1:1000), and β-actin (1:1000) at 4°C overnight. The membrane was washed, and the secondary antibody (1:15000) was added, incubated at room temperature for 1 hour, washed 3 times, and exposed by adding luminescent liquid. The chemiluminescence instrument was used for imaging, and the gray value of the protein band was analyzed by Image J software. The relative expression of the protein was calculated using β-actin as an internal reference.

[0063] Test results: To further explore the anti-tumor mechanism of dauricine, Western blot was used to detect the effects of different concentrations of dauricine on the expression of Notch3 and DLL4 proteins. Figures 15 to 19 Compared with the control group, the concentration of dauricine was concentration-dependent in the range of 0-30 μM. The above results showed that dauricine significantly inhibited Notch3 activity and reduced DLL4 expression to play an anti-liver cancer role.

[0064] The above experiments show that dauricine can inhibit the proliferation of non-small cell lung cancer by reducing mitochondrial membrane potential, inducing tumor cell apoptosis, promoting tumor cell necrosis, inhibiting the activity of Notch3 protein, and reducing the expression level of DLL4 protein, thereby playing an anti-lung cancer role. The above experimental results provide a theoretical reference for the development of dauricine as a natural anti-lung cancer drug.

Claims

1. The use of dauricine in the preparation of a drug for treating non-small cell lung cancer, characterized in that: Dauricine inhibits the proliferation of non-small cell lung cancer cells by reducing mitochondrial membrane potential, inhibiting Notch3 protein activity, and / or reducing the expression level of DLL4 protein.

2. The use according to claim 1, characterized in that: Dauricine inhibits the proliferation of non-small cell lung cancer cells by reducing mitochondrial membrane potential and inducing tumor cell apoptosis.

3. The use according to claim 2, characterized in that: Dauricine inhibits the proliferation of non-small cell lung cancer cells by reducing mitochondrial membrane potential and inducing tumor cell necrosis.

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