Application of T5224 in inhibiting invasion and metastasis of liver cancer

Abstract

The present invention belongs to the field of biomedicine, and specifically relates to the application of T5224 in inhibiting the invasion and metastasis of liver cancer. Specifically, the present invention provides the application of T5224, a small molecule compound targeting MAP1S, in treating MAP1S-related diseases, specifically, the MAP1S-related diseases include liver cancer, liver cancer metastasis, diseases caused by hepatitis B virus, etc.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine, and specifically relates to the application of T5224 in inhibiting the invasion and metastasis of liver cancer. Background Art

[0002] Primary liver cancer is the sixth most common cancer and the fourth leading cause of cancer death worldwide. From 2007 to 2016, the incidence of liver cancer increased by 2% to 3% per year, and the mortality rate also rose rapidly. In recent years, it has gradually stabilized, but liver cancer is still one of the malignant tumors with the lowest 5-year survival rate (18%). In 2020, there were more than 900,000 new cases of primary liver cancer and about 830,000 deaths. It is estimated that after 2025, the number of liver cancer patients worldwide will exceed 1 million per year.

[0003] Hepatocellular carcinoma (HCC) is the most common pathological type of primary liver cancer and one of the most common malignant tumors in the world, ranking third in the cause of cancer-related deaths worldwide. HCC mainly occurs on the basis of chronic hepatitis and cirrhosis. Hepatitis B virus (HBV) infection is its main risk factor. my country is a country with a high incidence of hepatitis B virus (HBV) infection. The social burden caused by liver cancer caused by HBV infection is particularly serious. Every year, up to 300,000 patients die from liver cancer caused by cirrhosis due to HBV infection. In recent years, although great progress has been made in HCC detection and curative treatments such as liver resection and liver transplantation, which have greatly prolonged the survival of early primary HCC patients, the frequent recurrence of HCC has greatly reduced the survival rate of patients. The recurrence rate of HCC within 1 year after liver resection is 35% and within 5 years is 70%. Compared with external tumor microenvironment factors, it plays a more important role in the invasion and metastasis of HCC cells. The successful metastasis of tumors depends on the invasion and migration of tumor cells. Invasion occurs at the tumor-host interface, where tumors interact with stromal cells to modulate the local extracellular membrane (ECM) to promote tumor cell migration. The core event is the dynamic changes in tumor cytoskeletal components that promote signal transduction and cell migration.

[0004] Currently available treatments are insufficient to address the need for effective treatments that can be used to treat the majority of individuals affected by liver cancer. Therefore, there is an urgent need to develop markers that predict early recurrence of liver cancer and targeted inhibitors thereof, in order to diagnose and treat early, improve the quality of life of patients, and prolong the survival of patients. Due to the stage of the patient's disease and / or the lack of available Summary of the invention

[0005] The present invention screened out a small molecule compound T5224 targeting MAP1S, providing a new target and treatment plan for the targeted treatment of MAP1S-related diseases.

[0006] In a first aspect, the present invention provides the use of a reagent for detecting MAP1S in the preparation of a product for diagnosing liver cancer, evaluating the invasiveness of liver cancer cells, and predicting the prognosis of liver cancer patients.

[0007] Preferably, the reagent is a reagent for detecting the MAP1S cell positivity rate and / or expression level.

[0008] The detection of the present invention includes evaluating whether the expression of the marker exists in the subject-derived sample and measuring its content (which can be an effective amount), including the derived qualitative results or quantitative concentration levels. The markers concerned by the present invention include MAP1S.

[0009] Preferably, the reagent for detecting expression level includes a reagent for detecting protein expression level and / or mRNA expression level.

[0010] Preferably, the reagents for detecting protein expression include reagents used in the following methods: hematoxylin-eosin staining (HE staining), safranin O-fast green staining, protein blotting (Western Blot method), enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), sandwich assay, immunohistochemistry (Immunohistochemistry) staining method, mass spectrometry, immunoprecipitation analysis, complement fixation analysis, flow cytometry fluorescence resolution technology and protein chip method.

[0011] Preferably, the reagents for detecting the mRNA expression amount include reagents used in the following methods: PCR-based detection method, Southern hybridization method, Northern hybridization method, dot hybridization method, fluorescence in situ hybridization method, DNA microarray method, ASO method, and high-throughput sequencing platform method.

[0012] Preferably, the reagents for measuring the protein level of MAP1S include reagents required for immunological detection.

[0013] Preferably, the immunological detection includes ELISA detection, Elispot detection, Western blotting or surface plasmon resonance. The reagents required for immunological detection are well known in the art, including but not limited to antibodies and targeting polypeptides that can specifically bind to MAP1S.

[0014] The "sample" mentioned in the present invention is preferably a biological sample separated from a subject, and may include but is not limited to whole blood, serum, plasma, tissue biopsy, cytological samples, platelets, reticulocytes, leukocytes, epithelial cells, whole blood cells, etc.

[0015] In a specific embodiment, the sample is a sample that may be fresh or frozen, including processed samples, such as tissue sections.

[0016] Preferably, the prognostic indicators include objective response rate (ORR), overall survival rate (OS), progression-free survival (PFS), time to progression (TTP), disease-free survival (DFS), time to treatment failure (TTF), response rate (RR), complete response (CR), partial response (PR), etc.

[0017] Preferably, cancer cells with low MAP1S expression are less invasive, and the probability of recurrence and metastasis are reduced. Patients with low MAP1S expression in cancer cells will have a better prognosis, for example, a longer overall survival rate.

[0018] On the other hand, the present invention provides the use of a MAP1S inhibitor in the preparation of a drug for treating liver cancer or inhibiting liver cancer metastasis.

[0019] As used herein, the term "inhibitor" refers to a substance that targets, reduces or inhibits at least one activity of a specific target gene or protein. In the present invention, it particularly refers to an active substance that targets, reduces or inhibits MAP1S. The inhibitor includes nucleic acid inhibitors, protein inhibitors, proteolytic enzymes, and protein binding molecules.

[0020] Preferably, the inhibitor includes those synthesized artificially or those existing in nature.

[0021] Preferably, the inhibitor includes an agent that reduces the expression of the target gene or protein through the following technologies: RNA interference technology (RNAi), antisense oligonucleotide (ASO) technology, CRISPR technology, TALEN technology, ZFN technology, Cre-loxP gene recombination technology.

[0022] Preferably, the inhibitor also includes compounds (including small molecule compounds) and antibodies that specifically target target genes or proteins.

[0023] The "antibodies" of the present invention include human antibodies, humanized antibodies, chimeric antibodies, multispecific antibodies, monoclonal antibodies, polyclonal antibodies and oligomers or antigen-binding fragments thereof. It also includes proteins with antigen-binding fragments or regions, such as Fab, Fab', F(ab')2, Fv, diabodies, Fd, dAb, large antibodies, single-chain antibody molecules, complementary determining region (CDR) fragments, scFv, diabodies, triabodies, tetrabodies and polypeptides, which contain at least a portion of an immunoglobulin sufficient to confer specific antigen binding to a target polypeptide.

[0024] The antibodies according to the present invention may be from any animal origin, including birds and mammals. Preferably, the antibodies are from human, mouse, donkey, monkey, rabbit, goat, guinea pig, camel, horse or chicken.

[0025] Preferably, the MAP1S inhibitor is T5224.

[0026] Preferably, the drug also contains a chemotherapeutic agent or a biological agent (such as an antibody) that specifically targets liver cancer. The term "chemotherapeutic agent" includes alkylating agents, antimetabolites, antitumor antibiotics, antitumor plant drugs and miscellaneous. Chemotherapeutic agents that are considered to be applicable include adriamycin, 5-fluorouracil (5FU), etoposide (VP-16), camptothecin, actinomycin D, mitomycin C, cisplatin (CDDP) and hydrogen peroxide.

[0027] In another aspect, the present invention provides use of a MAP1S inhibitor in the preparation of a therapeutic drug for a MAP1S-related disease.

[0028] Preferably, the MAP1S inhibitor is T5224, whose CAS number is 530141-72-1.

[0029] Preferably, the MAP1S-related diseases include cancer and diseases caused by hepatitis B virus.

[0030] The types of cancer described in this specification are not particularly limited. Specific examples include thyroid cancer, esophageal cancer, breast cancer, gastric cancer, pancreatic cancer, lung cancer, liver cancer, gallbladder cancer, rectal cancer, malignant melanoma, malignant lymphoma, osteosarcoma, pheochromocytoma, head and neck cancer, uterine cancer, ovarian cancer, chronic myeloid leukemia, acute myeloid leukemia, kidney cancer, prostate cancer, testicular cancer, bladder cancer or sarcoma.

[0031] More preferably, the cancer is a cancer that highly expresses MAP1S.

[0032] Preferably, the cancer is liver cancer.

[0033] More preferably, the cancer is liver cancer that highly expresses MAP1S, which may be more aggressive.

[0034] Preferably, the diseases caused by the hepatitis B virus include acute hepatitis, chronic hepatitis, cirrhosis, liver failure, liver cancer, etc.

[0035] On the other hand, the present invention provides a method for diagnosing liver cancer, screening highly invasive liver cancer cells, and predicting the prognosis of liver cancer patients, wherein the method comprises detecting MAP1S.

[0036] More specifically, the expression level of MAP1S was detected.

[0037] Preferably, the expression level includes mRNA expression level or protein expression level.

[0038] In another aspect, the present invention provides a method for treating liver cancer and inhibiting liver cancer metastasis, comprising administering a MAP1S inhibitor to a patient.

[0039] In another aspect, the present invention provides a method of using a MAP1S inhibitor to treat a MAP1S-related disease, the method comprising administering the MAP1S inhibitor to a patient.

[0040] Preferably, the MAP1S inhibitor is T5224.

[0041] Preferably, the MAP1S-related diseases include cancer and diseases caused by hepatitis B virus.

[0042] Preferably, the cancer is liver cancer.

[0043] Preferably, the diseases caused by the hepatitis B virus include acute hepatitis, chronic hepatitis, cirrhosis, liver failure, liver cancer, etc.

[0044] The liver cancer described in the present invention includes hepatocellular carcinoma (HCC), cholangiocarcinoma and hepatoblastoma. The liver cancer metastasis includes metastasis to any location, including but not limited to metastasis to the lung, bone, lymph node, adrenal gland and brain.

[0045] The diseases caused by hepatitis B virus (HBV) described in the present invention refer to diseases or conditions caused or aggravated by hepatitis B virus infection, or diseases or conditions for which HBV infection is a risk factor; specific examples include acute hepatitis (including acute hepatitis B), chronic hepatitis (including chronic hepatitis B), cirrhosis, liver scarring (cirrhosis), liver cancer (including hepatocellular carcinoma), etc.

[0046] The treatment provided by the present invention can be administered in combination with any one or more of the following methods: liver transplantation, surgical resection, percutaneous ablation, chemotherapy (including chemoembolization), radiotherapy, antibody therapy, etc. The treatment method can be to prepare the MAP1S inhibitor of the present invention and a pharmaceutically acceptable excipient into tablets, capsules, granules, oral solutions, suspensions, injections, microspheres or liposomes according to conventional methods, and administer them topically, enterally or parenterally, intradermally, intramuscularly, intraperitoneally, intravenously, subcutaneously, intranasally, by inhalation, epidurally and orally, and the diluents include PBS, saline, DMSO, etc. The administration can be systemic or local.

[0047] The term "treat" as used herein refers to the complete or partial alleviation or reduction of a disease or condition or disorder or symptoms, adverse effects or consequences or phenotypes associated therewith. The desired therapeutic effect includes, but is not limited to, preventing the occurrence or recurrence of the disease, alleviating symptoms, reducing any direct or indirect pathological consequences of the disease, preventing metastasis, slowing the rate of disease progression, improving or alleviating the disease state, and alleviating or improving prognosis. The term does not mean to completely cure the disease or completely eliminate any symptom or effect or all symptoms or consequences.

[0048] The term "subject" as used herein refers to any animal (e.g., mammal), including but not limited to humans, non-human primates, rodents, etc., that is to be the recipient of a particular treatment. Generally, the terms "subject" and "patient" are used interchangeably herein when referring to human subjects. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] Figure 1 showed that high levels of MAP1S in liver cancer cells were associated with HCC metastasis and poor prognosis.

[0050] Figure 2 It was shown that high MAP1S expression was negatively correlated with recurrence-free survival of HCC patients.

[0051] Figure 3 The results of grading HCC invasiveness and metastasis risk based on MAP1S histological evaluation are shown.

[0052] Figure 4 It was shown that inhibition of MAP1S could suppress HCC cell invasion and migration.

[0053] Figure 5 It was shown that inhibition of MAP1S can reduce tumor volume.

[0054] Figure 6 The results showed that T5224 had an inhibitory effect on the expression of MAP1S protein and mRNA in LM3 cells.

[0055] Figure 7 The invasion ability of different concentrations of T5224 on LM3 cells is shown. DETAILED DESCRIPTION

[0056] The present invention is further described below in conjunction with specific embodiments, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes based on the technical solution and inventive concept of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.

[0057] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0058] Example 1: MAP1S expression is elevated in HCC and metastatic HCC

[0059] 1. Chip detection

[0060] The inventors used tissue microarray (HLivH060CD03, Shanghai Xinchao Biotechnology Co., Ltd., China, containing 2 normal liver tissues, 6 cirrhotic liver tissues, 13 matched distal livers, 30 adjacent liver cancers and primary HCC, and 19 distant metastatic HCC tissues) and anti-MAP1S antibody (Biorbyt, #orb251641, UK) to detect the expression of MAP1S by immunohistochemistry.

[0061] Figure 1 A is a representative image of MAP1S expression detected by microarray immunohistochemistry in liver samples. Figure 1 B is the expression intensity score, which is calculated as the product of staining intensity and positive rate.

[0062] Among them, the staining intensity is divided into:

[0063] 0: no specific staining of cells; 1+: weak staining of cells; 2+: moderate positive staining; 3+: strong and uniform positive staining of cells.

[0064] The positive rate is divided into:

[0065] 0 points: 0% of liver cancer cells are stained; 1 point: 1-25% of liver cancer cells are stained; 2 points: 25-50% of liver cancer cells are stained; 3 points: 51-75% of liver cancer cells are stained; 4 points: 76-100% of liver cancer cells are stained.

[0066] The final expression intensity score was used to evaluate the expression intensity of MAP1S: 0-4 points indicated low expression intensity, 5-8 indicated medium expression intensity, and 12 points indicated high expression intensity.

[0067] 2. HCC biopsy

[0068] Using anti-MAP1S antibody (Biorbyt, #orb251641, UK), the inventors also evaluated HCC biopsies from 26 HCC lesions, including matched HCC tumor body (TB) and invasive front (IF).

[0069] Figure 1 The upper image of C shows the invasive front (IF) of 26 primary HCC cases, and the lower image shows the tumor body (TB), both of which are representative images of immunohistochemical detection of MAP1S. Figure 1 D is the area of ​​MAP1S positive cells labeled by anti-MAP1S antibody. Figure 1 E is the integrated optical density (IOD) of MAP1S positive cells labeled with anti-MAP1S antibody.

[0070] The results showed that the expression of MAP1S in the tumor invasive front (IF) was significantly stronger than that in the tumor body (TB), indicating that the regional upregulation of MAP1S in tumor IF is similar to the higher level of MAP1S in metastatic HCC.

[0071] Example 2: Correlation between MAP1S and HCC prognosis

[0072] Survival analysis was performed using the UALCAN database (http: / / ualcan.path.uab.edu).

[0073] Figure 1 F is the overall survival (OS) curve of Kaplan-Meier survival analysis of HCC patients with high MAP1S expression (n=91) and low / medium expression (n=274). The results showed that in the 365 HCC patient cohort, high expression of MAP1S mRNA was significantly negatively correlated with survival (P=0.029), and higher MAP1S mRNA levels were closely associated with shorter overall survival.

[0074] Example 3: Correlation between high expression of MAP1S and recurrence-free survival of HCC patients

[0075] The proteomic data used in this study were from the HCC dataset published by Gao et al., which is stored in https: / / doi.org / 10.1016 / j.cell.2019.08.052.

[0076] For the analysis of differentially expressed proteins, we used Python language and scipy package (v1.7.3), and performed Wilcoxon rank sum test with a significance threshold of P < 0.05. Survival analysis was performed using lifeline package (v0.27.1), and visualization was performed using matplotlib package (v3.5.1) and seaborn package (v0.11.2). Statistical analysis was performed using GraphpadPrism version 9.4.1 (Graphpad Software Inc., San Diego, CA, USA). The significance of different expression analyses was determined using Welch's two-sample t-test. The data provided are presented as mean ± SD of at least three independent experiments. P < 0.05 was considered statistically significant.

[0077] Results Figure 2 The results showed that HCC patients with higher MAP1S levels had a shorter recurrence-free survival (RFS) (P=0.019, HR=1.86 (1.10-3.15)), that is, high expression of MAP1S in HCC cells promoted HCC invasion and metastasis.

[0078] Example 4: Determination of HCC invasiveness and metastasis risk based on MAP1S histological evaluation results

[0079] The results showed that the expression of MAP1S was positively correlated with the invasiveness and metastasis of HCC, but negatively correlated with the survival of HCC patients. Therefore, detecting the expression of MAP1S in liver tissue can provide a diagnostic basis for determining the degree of HCC differentiation and provide a predictive indicator for the diagnosis, treatment and prognosis of HCC patients.

[0080] The specific determination process is as follows: Immunohistochemistry (IHC) staining: The liver cancer tissue samples are immunostained and specific antibodies are used to detect the expression level of MAP1S protein. Observation of staining results: Based on the staining results, the expression intensity of MAP1S in liver cancer tissue is evaluated. Usually, light microscopy is used for observation and scoring is performed based on the intensity of staining.

[0081] Staining intensity grading:

[0082] Grade 0: No obvious MAP1S protein expression. There is no observable MAP1S protein expression in cancer cells.

[0083] Grade 1+: MAP1S protein expression is very weak. There is very little MAP1S protein expression in the cytoplasm of cancer cells.

[0084] Grade 2+: Moderate expression of MAP1S protein. Moderate levels of MAP1S protein are expressed in the cytoplasm of cancer cells.

[0085] Grade 3+: MAP1S protein expression is very strong. There is obvious MAP1S protein expression in the cytoplasm and nucleus of cancer cells.

[0086] Based on the results of MAP1S histological assessment, the risk of HCC invasiveness and metastasis can be divided into: negative (grade 0, i.e. low grade), positive (grade 1+, grade 2+, i.e. intermediate grade), and strongly positive 10 (grade 3+, i.e. high grade). Figure 3 .

[0087] Example 5: Targeting MAP1S to treat diseases

[0088] 1. Effects of MAP1S knockdown on growth and invasion of liver cancer cells

[0089] To gain a deeper understanding of the effects of MAP1S expression on tumor cell growth and invasion, the inventors conducted in vitro experiments using low-invasive liver cancer cell lines HepG2 and MHCC97L and highly invasive HCC cell line HCCLM3.

[0090] Figure 4 A is a representative graph and statistical results of Western Blotting (WB) detection of MAP1S expression in HepG2, MHCC97L, and HCCLM3 cells. The invasiveness of liver cancer cell lines HepG2, MHCC97L, and HCCLM3 ranges from low to high. It was found that with the increase in invasiveness, MAP1S expression gradually increased, and MAP1S was highly expressed in HCCLM3 cells. Compared with HepG2 and MHCC97L, immunoblotting detection found that HCCLM3 expressed higher levels of MAP1S.

[0091] To verify the effect of MAP1S expression on HCC cell migration, the inventors constructed a lentiviral vector pLV-hU6-MAP1S shRNA01(human)-hef1a-mNeongreen-P2A-Puro, referred to as ShMAP1S, for knocking down MAP1S, wherein the shRNA sequence of the MAP1S gene is: 5'-GCAACCTTGATGAACAGCTCACGAATGAGCTGTTCATCAAGGTTGC-3'.

[0092] Using an empty vector without shRNA sequence (referred to as ShVector) as a control, ShVector and ShMAP1S were transfected into HCCLM3 cells (labeled as ShVector HCCLM3 and ShMAP1S HCCLM3, respectively), and the knockdown effect of MAP1S expression was confirmed by immunoblotting analysis.

[0093] Then the inventors performed a cell invasion test. The matrix gel-coated transwell (354480#, Corning, USA) was taken out from the -80°C refrigerator and placed at 4°C overnight for use. 500 μl of serum-free medium / chamber was taken and placed in a 37°C incubator for 2 hours. The target cells were digested and ShVector HCCLM3 and ShMAP1S HCCLM cell suspensions to be tested for invasion were prepared. Wash the cells three times with serum-free medium and count; add 100 μl of cell suspension to each well; pick up the chamber with tweezers, add 500 μl / well of DMEM medium containing 10%-20% fetal bovine serum, form a serum gradient inside and outside the chamber, and induce the cells to cross the chamber to the lower layer; culture in a 37°C incubator for 24 hours to wait for the target cells to cross the chamber; take out the Transwell chamber, wash twice with PBS, and fix the cells with 5% glutaraldehyde; add crystal violet (0.1%) to stain for 10 minutes, rinse with PBS at room temperature until the color does not change, repeat three times, then wipe off the cells that failed to invade above the chamber with cotton balls, and observe and record the cell number under a microscope.

[0094] Results Figure 4 B, C; among them, Figure 4 B is a representative picture and statistical results of WB detection of MAP1S expression in two transfected cells. Figure 4 C is the invasiveness of the two transfected cells detected by transwell (N=3) and the statistical results. The experiment showed that the invasion and migration ability of HCCLM3 cells with MAP1S knockdown were significantly reduced compared with the control cells.

[0095] 2. Animal experiments

[0096] In order to analyze the effect of MAP1S expression on the growth and invasion of liver cancer cells in vivo, the inventors conducted a mouse tumor-bearing experiment. All nude mice were randomly divided into groups, with 6 mice in each group, which were male 4-week-old Balb / c nude mice.

[0097] Construction of nude mouse tumor model:

[0098] Experimental group: ShMAP1S HCCLM3 cells,

[0099] Control group: ShVector HCCLM3 cells,

[0100] The above cells were resuspended in pre-cooled serum-free DMEM and the concentration was adjusted to 5×10 715 / ml, 200 μL was taken and slowly injected subcutaneously into each nude mouse. The nude mice were anesthetized for small animal imaging (KODAK In-Vivo Imaging System FX Pro, USA) on the 5th, 15th, 25th and 35th days respectively to detect tumor implantation and metastasis. The nude mice were then killed and some tumor tissues were frozen in liquid nitrogen.

[0101] Results Figure 5 . Figure 5 After mice were injected with ShMAP1S-HCCLM3 and control group cells, the changes in tumor volume over time (4 weeks) (upper left figure), the average diameter of the tumor (lower left figure), and the quantitative graph of tumor size (right figure) were shown. The results showed that compared with the control cells, MAP1S knockdown HCCLM3 cells resulted in significantly smaller tumor volume, or even no tumor formation (P<0.05).

[0102] In summary, inhibition of MAP1S can inhibit the growth and invasion of HCC cells both in vitro and in vivo.

[0103] Example 6: Effects of T5224 on MAP1S and liver cancer cells

[0104] T5224 targeting MAP1S was screened for subsequent experiments.

[0105] The mRNA and protein expression levels of MAP1S were detected in LM3 cells treated with different concentrations of T5224 (MCE, HY-12270). Figure 6 .

[0106] 2.5 μM T5224 was added to LM3 cells, and DMSO was added as a negative control. The cells were incubated for 24 hours at 37°C in a 5% CO2 incubator. The cells were then lysed and the proteins were collected. Immunoblotting was performed with anti-MAP1S antibody (1:1,000; GeneTex, USA), and the staining intensity was quantitatively detected using ImageQuant-TL-7.0 software version 2010 (Amersham Biosciences, Piscataway, NJ, USA). It was found that T5224 significantly reduced the expression of MAP1S protein in HCCLM3 cells (P < 0.05) (see Figure 7 ).

[0107] The above results prove that T5224 can reduce the expression of MAP1S in liver cancer cells and significantly inhibit the invasive ability of liver cancer cells.

[0108] The above contents are further detailed descriptions of the present invention in combination with specific preferred embodiments, and it cannot be determined that the specific implementation of the present invention is limited to these descriptions. For ordinary technicians in the technical field to which the present invention belongs, several simple deductions or substitutions can be made without departing from the concept of the present invention, which should be regarded as falling within the protection scope of the present invention.

Claims

1. Use of a MAP1S inhibitor in the preparation of a drug for treating hepatocellular carcinoma or inhibiting the metastasis of hepatocellular carcinoma, characterized in that: The MAP1S inhibitor is a shRNA that specifically targets MAP1S; The sequence of the shRNA specifically targeting MAP1S is GCAACCTTGATGAACAGCTCACGAATGAGCTGTTCATCAAGGTTGC.

2. The use according to claim 1, characterized in that: The drug also contains a chemotherapeutic agent or a biological agent that specifically targets hepatocellular carcinoma.

3. The use according to claim 1, characterized in that: The hepatocellular carcinoma metastasis includes metastasis to the lung, bone, lymph nodes, adrenal glands, and brain.

Images