Application of sophoramine as an autophagy inducer for inhibiting anaplastic thyroid cancer cells

Abstract

The application discloses application of sophoramine as an autophagy inducer for anaplastic thyroid cancer cells, and the sophoramine can promote autophagy of the anaplastic thyroid cancer cells by inhibiting an AKT / mTOR pathway, inhibit proliferation of the anaplastic thyroid cancer cells, and further promote death of tumor cells. The application provides a new theory and experimental basis for treating anaplastic thyroid cancer, simultaneously provides a new antitumor pathway for the anaplastic thyroid cancer, and potential of the sophoramine as a clinical auxiliary drug.

Description

(I) Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to the application of sophorogenin as an autophagy inducer for undifferentiated thyroid cancer cells. (II) Background Technology

[0002] Thyroid cancer is a common malignant tumor of the endocrine system, and its incidence has increased significantly in recent years. Among thyroid cancers, anaplastic thyroid carcinoma (ATC) has the worst prognosis and is the most aggressive subtype of thyroid cancer. The median survival of ATC is only 4-6 months. Although its incidence accounts for only about 5% of all thyroid tumors, it is extremely deadly and prone to recurrence. Currently, there is no effective treatment for patients with distant metastases. In clinical practice, surgical resection, targeted therapy, and radiotherapy can benefit patients in relatively good health, but the mortality rate due to cancer recurrence remains close to 100%.

[0003] my country has abundant traditional Chinese medicine resources. As a new source of anti-cancer drugs that is receiving increasing attention, Chinese medicine has the advantages of fewer toxic side effects, multiple therapeutic targets, and the ability to improve the adverse reactions of tumor chemotherapy. With the discovery of active ingredients in Chinese medicine and the continuous exploration of anti-tumor mechanisms, the integration of Chinese and Western medicine is becoming a new trend in cancer prevention and treatment in modern society.

[0004] Sophora tonkinensis Gagnep., also known as Guangdong sophora root, is the dried root and rhizome of the legume Sophora tonkinensis Gagnep., mainly produced in Yunnan, Guizhou, and Guangxi provinces. It is known for its heat-clearing, detoxifying, swelling-reducing, and throat-soothing effects. Sophoranone is a natural compound belonging to the isoflavone class. Extracted from Sophora tonkinensis root, it is widely used in traditional Chinese medicine prescriptions and possesses anti-inflammatory, antibacterial, antioxidant, and antitumor pharmacological effects. Some literature reports that sophoranone has significant antitumor activity in liver cancer cells, but there have been few reports on sophoranone in recent years, and its effects on undifferentiated thyroid carcinoma have never been reported.

[0005] Autophagy is an important intracellular catabolic process. Misfolded, damaged, denatured, or senescent proteins or organelles are enclosed in a double membrane and then fuse with lysosomes. Under the action of lysosomal acidic hydrolases, they are broken down into smaller molecules such as amino acids, which are then recycled and reused by the cell. In the early stages of tumorigenesis, autophagy can maintain cellular homeostasis and inhibit tumor development. Furthermore, autophagy can promote tumor apoptosis and inhibit tumor cell migration and invasion. In many mouse models, knocking out autophagy-related genes leads to accelerated tumor development. Therefore, promoting autophagy may be an adjunctive therapy for tumors. Reports have shown that inhibiting the expression of the PI3K / AKT / mTOR pathway through autophagy agonists such as rapamycin promotes autophagy, helps tumor cells form autophagosomes, and enhances tumor cell apoptosis. Therefore, further investigation into the specific mechanisms by which drugs induce autophagy in undifferentiated thyroid carcinoma can help provide more precise new strategies for prevention and treatment of cancer patients. (III) Summary of the Invention

[0006] The purpose of this invention is to provide an application of sophora root extract as an autophagy inducer for undifferentiated thyroid cancer cells. Sophora root extract can promote autophagy in undifferentiated thyroid cancer cells by inhibiting the AKT / mTOR pathway, inhibit the proliferation of undifferentiated thyroid cancer cells, and thus promote tumor cell death.

[0007] The technical solution adopted in this invention is:

[0008] This invention provides the application of sophoraginol as an autophagy inducer for undifferentiated thyroid carcinoma, wherein the inducer can promote autophagy in undifferentiated thyroid carcinoma cells.

[0009] Furthermore, the inducer promotes autophagy in undifferentiated thyroid cancer cells by inhibiting the AKT / mTOR pathway, thereby promoting tumor cell death.

[0010] This invention also provides the application of sophorabolic oleracea extract in the preparation of a drug for treating undifferentiated thyroid carcinoma.

[0011] Furthermore, the drug can inhibit the proliferation of undifferentiated thyroid cancer cells.

[0012] The structural formula of the sophoropogonin is:

[0013]

[0014] Compared with the prior art, the beneficial effects of the present invention are mainly reflected in:

[0015] This invention provides a novel application of sophora root extract as an autophagy inducer for undifferentiated thyroid carcinoma. Sophora root extract can regulate tumor cell autophagy by inhibiting the AKT / mTOR pathway, thereby inhibiting the proliferation of undifferentiated thyroid carcinoma cells. This provides new theoretical and experimental evidence for the treatment of undifferentiated thyroid carcinoma, while also providing a novel anti-tumor pathway for undifferentiated thyroid carcinoma and the potential of sophora root extract as a clinical adjuvant drug. (iv) Description of the attached drawings

[0016] Figure 1 The image shows the inhibitory effect of sophorabolic sorbitol on thyroid cancer cell lines; A represents the relative cell viability curves of different thyroid cancer cell lines after treatment with sophorabolic sorbitol; B represents the scratch assay micrographs of 8505C and KMH-2 cells after treatment with sophorabolic sorbitol; C represents the cloning assay micrographs of different thyroid cancer cell lines after treatment with sophorabolic sorbitol; and D represents the migration assay micrographs of 8505C and KMH-2 cells after treatment with sophorabolic sorbitol.

[0017] Figure 2 The results show the experimental findings of autophagy induced by sophora root extract in ATC cells. Figure A represents the cell viability of 8505C and KMH-2 cells after pretreatment with the necrosis-apoptosis inhibitor Necrostatin-1 (Nec-1) and the apoptosis inhibitor Z-VAD-FMK (Z-Vad-Fmk) followed by reversal of sophora root extract treatment. Figure B represents the microscopic images of 8505C and KMH-2 cells after sophora root extract treatment. Figure C represents the cell viability of 8505C and KMH-2 cells after pretreatment with the autophagy inhibitor chloroquine (CQ) followed by reversal of sophora root extract treatment. Figure D represents the fluorescence staining image after sophora root extract treatment.

[0018] Figure 3 The results of an experimental study on the effects of sophagogonin on autophagy-related proteins in ATC cells. (V) Detailed Implementation

[0019] The present invention will be further described below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto:

[0020] Unless otherwise specified, all methods described herein are conventional methods. All raw materials, unless otherwise specified, are commercially available. Quantitative experiments in the following examples were performed in triplicate, and the results were averaged. The room temperature described in this invention is 25-30°C.

[0021] Example 1, Materials and Methods

[0022] 1. Drugs and reagents

[0023] Sophorabolic oleoresin was purchased from Sichuan Cuiyirun Biotechnology Co., Ltd., and dimethyl sulfoxide (DMSO) was purchased from BBI (Shanghai, China). Sophorabolic oleoresin was prepared as a 100 mM stock solution using DMSO.

[0024] The CCK-8 assay kit was purchased from Novizan Biosciences. ER-Tracker Red (endoplasmic reticulum red fluorescent probe), Lyso-Tracker Red (lysosome red fluorescent probe), Mito-Tracker Green (mitochondrial green fluorescent probe), Western blotting and IP cell lysis buffer, BCA protein assay kit, and 5X Evo M-MLV RT Master Mix were all purchased from Beyotime Biotechnology Co., Ltd. The primary antibody Phospho-mTOR (Ser2448) (D9C2) was also used. Rabbit mAb#5536 (abbreviated as p-mTOR), Phospho-Akt (Ser473) (D9E) Rabbit mAb#4060 (abbreviated as p-AKT473), Phospho-Akt(Thr308)(D25E6) Rabbit mAb#13038 (abbreviated as p-AKT308), Phospho-4E-BP1 (Thr37 / 46)(236B4) Rabbit mAb#2855 (abbreviated as p-4EBP1), β-Actin (D6A8) Rabbit mAb#8457, Phospho-S6 Ribosomal Protein (Ser235 / 236)

[0025] Antibody #2211 (abbreviated as p-S6K S235 / 236), LC3B Antibody #2775 (including LC3B-Ⅰ / LC3B-Ⅱ), and goat anti-rabbit and goat anti-mouse secondary antibodies (lot number 7074S) were all purchased from CST Biotech, Inc., USA. All other consumables were purchased from BioSharp Corporation.

[0026] cell lines

[0027] Human undifferentiated thyroid carcinoma cell line 8505C was obtained from the German Collection of Microorganisms and Cell Cultures (Deutsche Sammlung von Mikroorganismen und Zellkulturen). Human undifferentiated thyroid carcinoma cell lines BHT101, CAL62, and KMH-2 were purchased from Procell LifeScience & Technology (Wuhan). All cells were STR certified and cultured in HyClone RPMI-1640 medium (hereinafter referred to as complete medium) containing 10% FBS, 100 U / mL penicillin, and 0.1 mg / mL streptomycin, in an incubator containing 5% CO2 at 37°C.

[0028] 2. Method

[0029] 2.1 Effects of Sophora tonkinensis extract on the activity of thyroid cancer cells

[0030] (1) CCK-8 assay for cell viability

[0031] Human thyroid undifferentiated cancer cells 8505C, BHT101, CAL62, and KMH-2 in the logarithmic growth phase were collected, with a cell count of 2 × 10⁻⁶ for each cell type. 3 Cells were seeded in 96-well cell culture plates containing 100 μL of complete culture medium per well. After cell attachment, the supernatant was discarded, and 200 μL of complete culture medium containing 0, 20, 25, 30, 35, 40, 45, 50, 55, and 60 μM sorbitol was added to the corresponding wells of the 96-well plates. A control group was prepared by adding 200 μL of complete culture medium containing an equal volume of 60 μM sorbitol (DMSO), and a blank control group was prepared by adding 200 μL of complete culture medium, with three replicates per group. The 96-well plates were incubated at 37°C with 5% CO2 for 48 h. Then, 10 μL of CCK-8 reagent was added to each well, and the plates were incubated at 37°C with 5% CO2 for 2 h. The absorbance (A) of each well was measured using a microplate reader at 450 nm. The 48-h cell viability was calculated as follows: viability % = (A / A) * (C ... 药物组 -A 空白组 ) / (A 对照组 -A 空白组 )×100%, the experiment was repeated 3 times.

[0032] (2) Scratch test

[0033] First, draw parallel lines evenly on the back of a 6-well plate using a pen and ruler, with a spacing of 0.5-1 cm between each line. Draw three horizontal lines per well to facilitate subsequent microscopic observation of each region. Undifferentiated thyroid cancer cells 8505C and KMH-2 in the logarithmic growth phase were collected, counted, and then cultured at a concentration of 2 × 10⁻⁶ cells / well. 5 Cells were seeded at a rate of 1000 μL / well in 6-well plates containing 2000 μL of complete culture medium. After cell attachment, a streak was made in the central region of cell growth using a micropipette tip, ensuring the streak intersects the bottom line. Cells in the central region were then removed. Each well of the 6-well plate was divided into a control group and two drug groups (30 μM and 35 μM). The control group received 2000 μL of complete culture medium, while the drug groups received 2000 μL of complete culture medium containing 30 μM and 35 μM succinate, respectively. Each group was divided into three replicates. The plates were incubated at 37°C with 5% CO2 for 0, 12, and 24 hours. The gaps between cells were photographed at 0, 12, and 24 hours and analyzed using an EVOS cell imaging system. TM Imaging was captured using the M7000 imaging system.

[0034] (3) Cloning experiment

[0035] Undifferentiated thyroid cancer cells 8505C, BHT101, CAL62, and KMH-2 in logarithmic growth phase were collected, counted, and then analyzed at a concentration of 5 × 10⁻⁶ cells / mL. 3 Cells were seeded at a rate of 1000 μL / well in 6-well plates containing 5000 μL of complete culture medium. After cell attachment, the culture medium was discarded. A control group and a drug group were set up. The drug group received 5000 μL of complete culture medium containing 25 μM, 30 μM, and 35 μM sophora flavescens extract, while the control group received 5000 μL of complete culture medium. Each group had 3 replicates. All groups were incubated in an incubator containing 5% CO2 at 37°C for approximately 14 days. When obvious colonies formed in the 6-well plates, culture was stopped and the old culture medium was discarded. After washing twice with PBS, 4% tissue fixative was added, and the cells were fixed at room temperature for 20 min. The fixative was discarded, and the cells were washed twice with PBS. Crystal violet was added for staining, and the cells were washed twice with PBS and the liquid was discarded. After air-drying at room temperature, the colonies were photographed using a Deli 15161S high-speed scanner (A3 soft pad / gray table).

[0036] (4) Migration and invasion experiments

[0037] Thirty minutes before the invasion assay, eight permeable cell culture chambers were placed in a 24-well plate. Mogengel Matrix matrix gel and HyClone RPMI-1640 medium were added to the upper chamber of four chambers at a volume ratio of 1:4. These four chambers were used for the invasion assay (one as the control group and three as the experimental group). The remaining four chambers were used for the migration assay (one as the control group and three as the experimental group). All eight chambers were grouped together for the cell migration and invasion assay.

[0038] Undifferentiated thyroid cancer cells 8505C and KMH-2 in logarithmic growth phase were collected, digested, and resuspended in HyClone RPMI-1640 medium for cell counting. Cells were then analyzed at a concentration of 5 × 10⁻⁶ cells / mL. 4 Cells were seeded into the upper chamber of all chambers. 800 μL of complete culture medium was added to the control group in the lower chamber. The experimental groups were seeded with 800 μL of complete culture medium containing 25 μM, 30 μM, and 35 μM sophora flavescens, respectively. All groups were incubated at 37°C with 5% CO2 for 24 h. Afterward, all chambers were removed, washed twice with PBS, and then fixed at room temperature for 20 min with 4% tissue fixative. The fixative was discarded, and the cells were washed twice with PBS, stained with crystal violet for 20 min, washed twice with PBS, and the liquid was discarded. After air-drying at room temperature, the cells were used in the EVOS cell imaging system. TM Images were captured by the M7000 imaging system.

[0039] 2.2 Experiment on the induction of autophagy in ATC cells by sophagosine

[0040] (1) Effects of Sophora flavescens extract on apoptosis inhibitors and necrosis inhibitors

[0041] Human thyroid undifferentiated cancer cells 8505C and KMH-2 in the logarithmic growth phase were collected, with a cell count of 2 × 10⁻⁶ for each cell type. 3Cells were seeded in 96-well cell culture plates containing 100 μL of complete culture medium per well. After cell adhesion, the supernatant was discarded, and 100 μL of complete culture medium containing 10 μM necrosis-apoptosis inhibitor Necrostatin-1 (Nec-1) and apoptosis inhibitor Z-VAD-FMK (Z-Vad) were added to the wells for drug pretreatment. The 96-well plates were incubated in an incubator with 5% CO2 at 37°C for 4 h. After the supernatant was discarded, 200 μL of complete culture medium containing 0, 30, 40, and 50 μM sophora flavescens were added to the corresponding wells for drug pretreatment, respectively. A control group was prepared by adding 200 μL of complete culture medium containing an equal volume of 50 μM sophora flavescens (DMSO), and a blank control group was prepared by adding 200 μL of complete culture medium. Each group had three replicates. After culturing 96-well plates at 37°C with 5% CO2 for 48 hours, 10 μL of CCK-8 reagent was added to each well, and the plates were incubated at 37°C with 5% CO2 for 2 hours. The absorbance (A) of each well was measured at 450 nm using a microplate reader. The viability of all cells after 48 hours was calculated as follows: viability % = (A / (A)) 药物组 -A 空白组 ) / (A 对照组 -A 空白组 )×100%, the experiment was repeated 3 times.

[0042] (2) Cell imaging experiment

[0043] Undifferentiated thyroid cancer cells 8505C and KMH-2 in logarithmic growth phase were collected, counted, and then stored at 2 × 10⁻⁶ cells per well. 5 Cells were seeded into 6-well plates. After cell attachment, the original culture medium was discarded, and 2000 μL of complete culture medium containing 50 μM sophora flavescens was added. The control group received 2000 μL of complete culture medium. The 6-well plates were incubated in an incubator containing 5% CO2 at 37°C for 24 h. The plates were then removed and placed in an EVOS cell imaging system. TM Imaging was captured using the M7000 imaging system.

[0044] (3) Effects of Sophora tonkinensis on autophagy inhibitors

[0045] Human thyroid undifferentiated cancer cells 8505C and KMH-2 in the logarithmic growth phase were collected, with a cell count of 2 × 10⁻⁶ for each cell type. 3Cells were seeded in 96-well cell culture plates containing 100 μL of complete culture medium per well. After cell attachment, the supernatant was discarded, and 100 μL of complete culture medium containing 10 μM chloroquine (CQ), an autophagy inhibitor, was added. The 96-well plates were incubated at 37°C with 5% CO2 for 4 h. After incubation, the supernatant was discarded, and 200 μL of complete culture medium containing 0, 30, 40, or 50 μM sorbitol was added. A control group was also included, with 200 μL of DMSO complete culture medium (equivalent to 50 μM sorbitol) added, and a blank control group was included, with three replicates per group. After culturing 96-well plates at 37°C with 5% CO2 for 48 hours, 10 μL of CCK-8 reagent was added to each well, and the plates were incubated at 37°C with 5% CO2 for 2 hours. The absorbance (A) of each well was measured at 450 nm using a microplate reader. The viability of all cells after 48 hours was calculated as follows: viability % = (A / (A)) 药物组 -A 空白组 ) / (A 对照组 -A 空白组 )×100%, the experiment was repeated 3 times.

[0046] (4) Confocal Experiment

[0047] Undifferentiated thyroid cancer cells 8505C and KMH-2 in the logarithmic growth phase were collected, counted, and then stored at 2 × 10⁻⁶ cells per well. 4 Cells were seeded into quarter-well dishes, with a volume of 2000 μL per well. After cell attachment, the culture medium was discarded, and 2000 μL of complete culture medium containing 50 μM sophora flavescens was added to each well. The control group received 2000 μL of complete culture medium. The quarter-well dishes were incubated in an incubator containing 5% CO2 at 37°C for 24 h. The culture medium in each well was discarded, and the cells in each well were fixed with 4% paraformaldehyde for 20 min. Then, 2000 μL of complete culture medium containing 5% endoplasmic reticulum tracer, lysosomal tracer, and mitochondrial tracer were added, respectively. The cells were incubated in the dark for 8 h, and the supernatant was discarded. The cells were washed with PBS and then imaged using a Stellaris Divive multiphoton microscope.

[0048] 2.3 Study on the effect of sophagosine on autophagy-related proteins in ATC cells

[0049] Undifferentiated thyroid cancer cells 8505C and KMH-2 in logarithmic growth phase were collected, counted, and then stored at 2 × 10⁻⁶ cells per well. 5Cells were seeded into 6-well plates at a volume of 2000 μL per well. After cell attachment, the original culture medium was discarded, and 2000 μL of complete culture medium containing 0, 30, 35, 40, 45, or 50 μM succinate was added to each well. The control group received 2000 μL of complete culture medium. The 6-well plates were incubated at 37°C with 5% CO2 for 24 h. After incubation, the plates were removed, and cells were digested with trypsin. Cells were collected by centrifugation, and the supernatant was discarded. Cells were then lysed using Western blotting buffer containing 10% protease inhibitor. Cells were lysed on ice for 20 min and then sonicated twice for 10 seconds each time using a 25W ultrasonicator. Protein was extracted from the supernatant by centrifugation, and protein concentration was determined using a biuret assay kit. Proteins were analyzed by FuturePAGE. TM Separation was performed using 4-20% 12-well gels, followed by transfer to PVDF membranes via a rapid transfer system. PVDF membranes were blocked with 5% skim milk at room temperature for 2 hours. All PVDF membranes were incubated at 4°C with primary antibodies (p-mTOR, p-AKT473, p-AKT308, p-4EBP1, β-Actin, p-S6K S235 / 236, LC3B-Ⅰ, LC3B-Ⅱ) for 8 hours, followed by washing with TBST and incubation at room temperature for 2 hours with goat anti-rabbit IgG, goat anti-mouse IgG, and monkey anti-goat antibodies. The target bands were pretreated using the FDbioDura ECL kit. Exposure and observation were performed using a ChemiDoc-MP imager.

[0050] 2.4 Statistical Analysis

[0051] All quantitative data were statistically analyzed using Graphpad Prism 9.0 software. Multivariate analysis of variance was used to compare the means among multiple groups. A p-value < 0.05 was considered statistically significant.

[0052] 3 Results and Analysis

[0053] 3.1 Sophora tonkinensis extract inhibits the proliferation of undifferentiated thyroid cancer cells.

[0054] Figure 1 The growth of different undifferentiated thyroid cancer cells after 48 hours of treatment with senna was shown in Figure A. Figure A indicates that senna significantly inhibits the growth of undifferentiated thyroid cancer cell lines, with varying degrees of sensitivity among different cell lines. 8505C and KMH-2 cells showed the best sensitivity to senna, and were therefore selected as the main cell types for this study. Simultaneously, scratch assays (B) and colony formation assays (C) showed that cell growth was significantly slowed under senna treatment. In the migration and invasion assay (D), the results indicated that senna significantly inhibited the migration ability of cancer cells, with the inhibitory effect increasing with increasing concentration.

[0055] 3.2 Sophora tonkinensis promotes autophagy formation in cells.

[0056] Cells treated with the apoptosis inhibitors Necrostatin-1 (Nec-1) and Z-VAD-FMK (Z-AD), followed by treatment with sophora tonkinensis, showed increased cell viability and reversed apoptosis. Figure 2 (A)

[0057] Autophagy helps tumor cells form autophagosomes and enhances tumor cell apoptosis. After 24 hours of treatment with sophagosine, we observed the production of autophagic vesicles in cells using microscopic imaging. Figure 2 (B) In Figure 2 Based on the results of the B study, we pretreated cells with the autophagy inhibitor Chloroquine (CQ) followed by treatment with sophagosine, and found that cell viability was also improved to some extent. Figure 2 (C). Subsequent endoplasmic reticulum and mitochondrial probes showed a significant increase in the number of endoplasmic reticulum and mitochondria, indicating the occurrence of endoplasmic reticulum autophagy and mitophagy. Lysosomal probes revealed a large increase in intracellular fluorescence intensity compared to the control group, indicating that after treatment with sophagosine, cells tend to form autophagosomes and use them to guide apoptosis. Figure 2 (D).

[0058] 3.3 Effects of Sophora tonkinensis on autophagy-related proteins

[0059] mTOR is a serine / threonine kinase belonging to the PI3K-associated kinase family, involved in the formation of mTORC1 and mTORC2. mTORC1 inactivates the autophagy regulatory complex formed by ULK1 and its interacting proteins through phosphorylation, thereby affecting autophagosome biogenesis. LC3B, a widely used autophagy marker, participates in multiple processes of autophagosome formation. During induced autophagy, LC3B is hydrolyzed by Atg4 protein to generate LC3-I. LC3-I is activated by Atg7 and then coupled intramembranously with phosphatidylethanolamine (PE) to generate processed LC3-II. The processed LC3-II is recruited to growing phagosomes.

[0060] To investigate the role of sophorogenin as an autophagy inducer in undifferentiated thyroid cancer cells, the protein levels of p-mTOR, p-AKT308, p-AKT473, p-4EBP1, p-S6K, LC3B-Ⅰ, and LC3B-Ⅱ were detected by Western blotting. Figure 3The results showed that phosphorylation of AKT308, AKT473, and EBP1 proteins inhibited the transduction pathways of signals related to cell survival and growth, indicating that cells gradually died. Inhibition of phosphorylated mTOR suppressed downstream phosphorylation of S6K protein, preventing its participation in downstream gene activation and regulation, and promoting autophagy. Significantly increased LC3B cleavage patterns with increasing concentration indicated that autophagy was observed with increasing concentration. Treatment with sophorazinon resulted in the downregulation of AKT / mTOR pathway-related proteins and the production of LC3B cleavage patterns. Sophorazinon induced autophagy through the AKT / mTOR pathway, leading to tumor cell death.

[0061] The above description of the embodiments is only for the purpose of helping to understand the method and core ideas of the present invention. It should be noted that those skilled in the art can make several improvements and modifications to the present invention without departing from the principles of the present invention, and these improvements and modifications also fall within the protection scope of the claims of the present invention.

Claims

1. The application of a sophoraginol as the sole active ingredient in the preparation of a drug for treating undifferentiated thyroid carcinoma.

2. The application as described in claim 1, characterized in that, The drug can inhibit the proliferation of undifferentiated thyroid cancer cells.

Images