Use of ttll1 inhibitors in the preparation of a medicament for alleviating and / or treating gastric cancer

Abstract

The application discloses application of a TTLL1 inhibitor in preparation of a medicine for relieving and / or treating stomach cancer, and belongs to the field of biomedical technology. The application discloses application of a TTLL1 expression inhibitor in preparation of a medicine for relieving and / or treating stomach cancer, and the expression of TTLL1 is down-regulated through the TTLL1 expression inhibitor, so that the proliferation activity and migration ability of stomach cancer cells can be effectively inhibited. The application further provides a complete scheme for preparing various dosage forms of medicines by using the TTLL1 expression inhibitor, and the technical scheme has good clinical transformation prospect and application potential as a new type of stomach cancer resisting medicine.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to the application of TTLL1 inhibitors in the preparation of drugs for alleviating and / or treating gastric cancer. Background Technology

[0002] Gastric cancer (GC) is one of the most common malignant tumors of the digestive system and a leading cause of cancer-related deaths worldwide. In China, the incidence and mortality rates of gastric cancer rank among the highest of all malignant tumors, seriously threatening people's lives and health. Currently, early-stage gastric cancer is mainly treated with endoscopic resection or radical surgery, often combined with chemotherapy, targeted therapy, and immunotherapy. However, due to the lack of specific early symptoms of gastric cancer, some patients are diagnosed at a locally advanced stage or with distant metastasis, thus losing the opportunity for radical surgery. For patients with intermediate-to-advanced or metastatic gastric cancer, while existing systemic therapies can prolong survival to some extent, the overall efficacy remains limited, and recurrence, metastasis, and drug resistance are common, resulting in poor prognosis. Therefore, further elucidating the key molecular mechanisms of gastric cancer development and progression, and developing new therapeutic targets and intervention strategies, remain crucial issues that urgently need to be addressed in the field of precision treatment for gastric cancer.

[0003] It is important to note that although both gastric cancer and hepatocellular carcinoma are common malignant tumors of the digestive system, they differ significantly in their specific causes, mechanisms of development, tumor microenvironment, and clinical treatment. Gastric cancer is typically associated with Helicobacter pylori infection, chronic atrophic gastritis, intestinal metaplasia, gastric mucosal dysplasia, dietary factors, and genetic susceptibility. Its typical progression is "chronic gastritis—atrophic gastritis—intestinal metaplasia—dysplasia—gastric cancer." In contrast, hepatocellular carcinoma is usually closely related to chronic hepatitis B virus infection, hepatitis C virus infection, long-term alcohol consumption, non-alcoholic fatty liver disease, aflatoxin exposure, and a background of cirrhosis. Its pathogenesis often involves a continuous pathological evolution of "chronic hepatitis—liver fibrosis—cirrhosis—liver cancer." Therefore, gastric cancer and liver cancer have different tissue origins, underlying disease backgrounds, and precancerous lesion evolution pathways.

[0004] From a pathogenesis perspective, gastric cancer primarily originates from gastric mucosal epithelial cells. Its development is closely related to gastric mucosal barrier disruption, chronic inflammation, abnormal epithelial cell differentiation, altered cell adhesion, destruction of gastric gland structure, and changes in the local gastric mucosal microenvironment. Hepatocellular carcinoma, on the other hand, typically occurs in a long-term chronic liver injury and regenerative environment. Hepatocytes repeatedly die, regenerate, and proliferate abnormally under continuous inflammatory stimulation, oxidative stress, liver fibrosis, and the microenvironment of cirrhosis, leading to genomic instability, cell cycle dysregulation, enhanced angiogenesis, and increased invasive and metastatic capabilities. The liver itself possesses unique metabolic functions, detoxification functions, blood supply characteristics, and an immune tolerance microenvironment, giving hepatocellular carcinoma its own characteristics in terms of molecular regulatory networks, tumor angiogenesis, immune escape, and treatment tolerance. Therefore, gastric cancer is not simply a different manifestation of hepatocellular carcinoma in different organs, but rather a type of malignant tumor with independent etiological basis, histological origin, and molecular pathological characteristics.

[0005] In terms of treatment options, gastric cancer and hepatocellular carcinoma also differ significantly. Gastric cancer treatment typically centers on gastrectomy and lymph node dissection, combined with a comprehensive strategy including perioperative chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Treatment decisions are largely based on factors such as the depth of gastric wall invasion, lymph node metastasis, distant metastasis, HER2 status, microsatellite instability, and PD-L1 expression. In contrast, hepatocellular carcinoma treatment options depend not only on tumor size, number, vascular invasion, and distant metastasis, but also heavily on the patient's liver function reserve, degree of cirrhosis, and portal hypertension. Clinical treatment methods include liver resection, liver transplantation, radiofrequency ablation, microwave ablation, transarterial chemoembolization, radiotherapy, targeted therapy, immunotherapy, and their combination therapies. Comparatively, the drug metabolism, treatment tolerance, local treatment methods, and prognostic assessment of gastric cancer differ significantly from those of hepatocellular carcinoma. Therefore, even if certain molecular targets or interventions may appear superficially similar in different tumors, their specific application basis, indications, environment of action, and therapeutic significance in gastric cancer remain distinct.

[0006] The TTLL1 (tubulin tyrosine ligase-like 1) gene is a protein-encoding gene, also known as the TTL family tubulin polyglutamylase complex subunit L1. It belongs to the TTL-like protein family and encodes a tubulin polyglutamylase complex-associated protein. TTLL1 primarily participates in the post-translational modification of tubulin, catalyzing or promoting polyglutamylation of tubulin, thereby regulating various biological processes such as microtubule structural stability, microtubule dynamics, cytoskeleton remodeling, and intracellular transport. The microtubule system is a crucial structural basis for maintaining cell morphology, cell polarity, chromosome segregation, mitosis, and cell migration. Tubulin polyglutamylation, as an important form of post-translational modification, affects the interaction between microtubules and motor proteins, microtubule-associated proteins, and other regulatory factors, playing a vital regulatory role in cell division, cell motility, and signal transduction. Abnormal TTLL1 function can lead to an imbalance in tubulin modification, thereby affecting cell cycle progression, cytoskeleton homeostasis, chromosome segregation, and cell migration and invasion capabilities.

[0007] Existing research indicates that abnormal microtubule structure and dynamics are key molecular characteristics of tumorigenesis and development. During rapid proliferation, invasion, metastasis, and treatment resistance, tumor cells often exhibit cytoskeleton remodeling, abnormal spindle assembly, increased chromosomal instability, and enhanced cell migration. The microtubule system is also a crucial target for many classic antitumor drugs; for example, taxanes and vinca alkaloids can inhibit tumor cell proliferation by interfering with microtubule polymerization or depolymerization. As a key molecule regulating tubulin polyglutamylation, although studies have revealed the basic biological functions of TTLL1 from the perspectives of tubulin polyglutamylation, cytoskeleton regulation, and cell motility, the specific role and molecular mechanisms of TTLL1 in the development of tumors, especially solid tumors such as gastric cancer, remain unclear. Currently, there is a lack of systematic research exploring the relationship between TTLL1-mediated microtubule modification abnormalities, cytoskeleton homeostasis changes, and gastric cancer cell proliferation, invasion, metastasis, and treatment sensitivity. Furthermore, there is a lack of intervention strategies and translational applications targeting TTLL1. Therefore, further research on the function of TTLL1 and its role in gastric cancer, especially the development of TTLL1 inhibitors for the preparation of drugs to alleviate and / or treat gastric cancer, is of great scientific significance and potential clinical value.

[0008] Therefore, developing a drug that targets TTLL1 to alleviate and / or treat gastric cancer has become an urgent need in this field. Summary of the Invention

[0009] The purpose of this invention is to explore the specific role of TTLL1 in gastric cancer and to provide a drug that targets TTLL1 to alleviate and / or treat gastric cancer.

[0010] In a first aspect, the present invention provides the use of a TTLL1 expression inhibitor in the preparation of a drug for alleviating and / or treating gastric cancer, wherein the TTLL1 expression inhibitor is shRNA; the nucleotide sequence of the shRNA is shown in SEQ ID NO: 1 and SEQ ID NO: 2.

[0011] In a second aspect, the present invention provides the use of a drug comprising a TTLL1 expression inhibitor in the preparation of a drug for alleviating and / or treating gastric cancer, wherein the TTLL1 expression inhibitor is a lentivirus comprising shRNA, the nucleotide sequence of which is shown in SEQ ID NO: 1 and SEQ ID NO: 2.

[0012] Preferably, the drug further includes pharmaceutically acceptable excipients; the dosage form of the drug is an injection.

[0013] This invention utilizes the datasets GSE84426, GSE13861, GSE29272, GSE84437, and GSE57303 from the Solid Tumor Biomarker Exploration Platform (BEST), which focus on gastric cancer research, to analyze the relationship between TTLL1 expression levels and overall survival and recurrence-free survival in gastric cancer patients. The analysis revealed that patients in the high TTLL1 expression group had significantly shorter overall survival and recurrence-free survival than those in the low TTLL1 expression group. Based on this bioinformatics analysis, TTLL1 was identified as a potential diagnostic biomarker and therapeutic target for gastric cancer.

[0014] This invention uses human gastric cancer HGC-27 cells as experimental subjects. Through knockdown experiments, it verifies the effect of shRNA lentivirus targeting TTLL1 on the expression level of TTLL1 protein, verifies the effect of TTLL1 inhibitors on the migration and proliferation of gastric cancer cells, and confirms the effect of TTLL1 inhibitors on the activity of human gastric cancer HGC-27 cells.

[0015] Compared with the prior art, the present invention has the following advantages: This invention, through large-scale bioinformatics analysis of clinical samples, demonstrates that the TTLL1 gene is specifically highly expressed in gastric cancer tissues, and that this high expression is significantly associated with poor patient prognosis. This reveals that the TTLL1 gene is a key factor in gastric cancer, suggesting that TTLL1 could serve as a potential diagnostic biomarker and therapeutic target for gastric cancer.

[0016] This invention experimentally validates that TTLL1 expression inhibitors can serve as drugs for alleviating and / or treating gastric cancer. Specifically, by specifically downregulating TTLL1 gene expression through lentiviruses carrying shRNA, significant anti-cancer effects can be generated in multiple aspects in an in vitro model.

[0017] This invention not only provides the theoretical basis for TTLL1 expression inhibitors as therapeutic agents for gastric cancer, but also offers a complete scheme for preparing drugs in various dosage forms. These technical solutions, as a novel class of anti-gastric cancer drugs, have promising prospects for clinical translation and application potential. Attached Figure Description

[0018] Figure 1 This is a graph showing the relationship between TTLL1 expression levels and overall patient survival, analyzed using datasets GSE84426, GSE13861, GSE29272, GSE84437, and GSE57303 in Example 1. Figure 2 This is a graph illustrating the relationship between TTLL1 expression levels and relapse-free survival in Example 1, based on the GSE13861 dataset. Figure 3 This is a graph showing the results of Western blot verification of the effect of TTLL1 inhibitor on TTLL1 protein expression level in HLF gastric cancer cells in Example 2; Figure 4 This is a cell cloning experiment diagram used in Example 3 to detect the effect of TTLL1 inhibitor on the proliferation ability of gastric cancer cells; Figure 5 This is a CCK-8 assay diagram used in Example 3 to detect the effect of TTLL1 inhibitors on the proliferation of gastric cancer cells. Figure 6 This is a scratch healing experiment diagram used in Example 4 to detect the effect of TTLL1 inhibitors on the migration ability of gastric cancer cells. Detailed Implementation

[0019] To better understand the present invention, the following embodiments are further illustrations of the invention, but the scope of the invention is not limited to these embodiments. Unless otherwise specified, the experimental methods used in the embodiments of the present invention are conventional methods. The reagents and materials used in the embodiments are all commercially available, and the quantitative experiments involved in the embodiments are all performed in at least three replicates.

[0020] Example 1: Bioinformatics Analysis of TTLL1 Expression and Prognostic Value in Gastric Cancer Using the BEST database (https: / / rookieutopia.hiplot.com.cn / app_direct / BEST / #PageHomeAnalysisModuleSelection), we analyzed the relationship between TTLL1 expression levels and overall survival in gastric cancer patients across the GSE84426, GSE13861, GSE29272, GSE84437, and GSE57303 datasets. Patients were divided into a high TTLL1 expression group and a low TTLL1 expression group using the median TTLL1 expression level as the grouping cutoff. Kaplan-Meier curves were plotted, and the Log-rank test was used to compare survival differences between the two groups. Statistical significance was indicated as follows: P<0.05; P<0.01; P < 0.001; when P < 0.05, the difference is considered statistically significant.

[0021] Using the same method, the difference in relapse-free survival between patients with high TTLL1 expression and those with low TTLL1 expression was analyzed in the GSE13861 dataset.

[0022] Overall survival time Figure 1 As shown, in the GSE84426, GSE13861, GSE29272, GSE84437, and GSE57303 datasets, the overall survival of patients in the TTLL1 high expression group was significantly shorter than that in the low expression group (Log-rank P<0.05). Relapse-free survival is as follows... Figure 2 As shown in the data, in the GSE13861 dataset, patients in the TTLL1 high expression group had significantly shorter recurrence-free survival than those in the low expression group (Log-rank P < 0.05). In conclusion, this indicates that high TTLL1 expression is associated with poor prognosis in gastric cancer patients, suggesting that TTLL1 may serve as a potential diagnostic biomarker and therapeutic target for gastric cancer.

[0023] Example 2: Construction of shRNA lentiviral vector targeting TTLL1 and establishment of stable knockdown cell lines 1. shRNA sequence design and synthesis A specific shRNA interference fragment was designed targeting the human TTLL1 (Gene ID: 25809) mRNA sequence. Its template sequence is as follows: Justice Chain (SEQ ID NO: 1): GTTTGTGTCTCAATCTAATAAttcaagagaTTATTAGATTGAGACACAAAC; Antisense chain (SEQ ID NO: 2): CAAACACAGAGTTAGATTATTaagttctctAATAATCTAACTCTGTGTTTG.

[0024] 2. Construction of lentiviral vectors After annealing the synthesized double-stranded oligonucleotides to form double strands, they were cloned into the pLV3-U6-MCS-shRNA-CopGFP-Puro lentiviral vector (Wuhan Miaoling Biotechnology Co., Ltd., catalog number P29436) which had been double-digested with AgeI and EcoRI, to construct the recombinant plasmid pLV3-U6-TTLL1(human)-shRNA1-CopGFP-Puro (Wuhan Miaoling Biotechnology Co., Ltd., catalog number P105476). The correctness of the inserted sequence was verified by colony PCR and sequencing.

[0025] 3. Lentiviral packaging The virus was packaged using a three-plasmid system. Healthy 293T cells were seeded in 10 cm culture dishes. When the cell density reached 70%-80%, the following plasmids were co-transfected using liposome transfection: 8 μg of pLV3-U6-TTLL1(human)-shRNA1-CopGFP-Puro (or the empty control plasmid pLV3-U6-MCS-shRNA-CopGFP-Puro), 6 μg of the packaging plasmid psPAX2, and 2 μg of the envelope plasmid pMD2.G. Six hours after transfection, the medium was replaced with complete medium (DMEM liquid medium + 10% fetal bovine serum FBS). After 48 h and 72 h of culture, the virus-containing supernatant was collected, filtered through a 0.45 μm filter, and the virus was concentrated by ultracentrifugation to obtain lentiviral particles (i.e., the TTLL1 inhibitor), which were then stored at -80℃.

[0026] 4. Cell infection and screening Human gastric cancer HGC-27 cells were seeded in 6-well plates (5 × 10⁻⁶ cells / well). 5Cells were cultured in / wells until the density reached approximately 30%. Viral supernatant (MOI=10) and polybrene transfection reagent at a final concentration of 5 μg / mL were added. After 24 h of infection, the medium was replaced with fresh complete medium and cultured for another 48 h. Puromycin was then added at a final concentration of 2 μg / mL for selection, continuing for approximately one week until all untransfected control cells died. Monoclonal cell lines were obtained using limiting dilution, and green fluorescence expression was observed under a fluorescence microscope to assess infection efficiency. Finally, a stable TTLL1 knockdown shTTLL1 cell line and an empty vector control shNC cell line were obtained.

[0027] 5. Low-efficiency verification Total protein was extracted from shTTLL1 and shNC cells and Western blot was performed to verify the knockdown effect of TTLL1 protein.

[0028] Prepare the protein extraction buffer according to the following ratio: RIPA lysis buffer: 1 mL; 50× protease inhibitor: 20 μL; 100× phosphatase inhibitor A: 10 μL; 100× phosphatase inhibitor B: 10 μL; 100× PMSF protease inhibitor: 10 μL. Mix well and use on ice.

[0029] Discard the culture medium and wash with PBS; add protein extraction buffer to lyse the cells for 5 min and collect with a scraper; then sonicate to disrupt the cells, and incubate the lysate on ice for 10 min. Centrifuge at 12000 rpm and 4℃ for 10 min, and collect the supernatant as total cell protein.

[0030] Mix total cellular protein with 5× loading buffer at a ratio of 4:1, and heat at 100℃ for 5 min to denature the protein; the protein sample can be directly used for electrophoresis after cooling to room temperature.

[0031] Place the pre-prepared SDS-PAGE gel into the electrophoresis tank and add electrophoresis buffer; add protein samples and pre-stained molecular weight markers to the upper sample wells. Electrophoresis is performed at 80 V, and after the samples enter the separating gel, the voltage is adjusted to 120 V. Electrophoresis is stopped when the bromophenol blue reaches near the bottom of the gel.

[0032] Cut the polyvinylidene fluoride (PVDF) membrane and activate it with methanol before placing it in the transfer buffer. Assemble the gel and PVDF membrane in the order of sponge-filter paper-gel-membrane-filter paper-sponge and place it in a wet transfer apparatus. Transfer the membrane at 4°C and 200 mA for 60 min.

[0033] After transfer, the membrane was washed with TBST buffer and blocked with TBST buffer containing 10% skim milk powder for 2 hours. Then, diluted primary antibody (TTLL1 Polyclonal Antibody, Invitrogen, catalog number PA5-27285) was added and incubated overnight at 4°C. After washing, HRP-labeled secondary antibody was added and incubated at room temperature for 1 hour, followed by another wash. The membrane was then placed in an ECL chemiluminescent substrate for development and exposed in an imaging system to acquire band images.

[0034] Western blotting results are as follows: Figure 3 As shown, compared with the shNC group, the expression level of TTLL1 protein in shTTLL1 cells was significantly inhibited (P<0.01), and the expression level of internal control GAPDH was similar in both groups, indicating that this embodiment successfully constructed a shRNA lentivirus targeting TTLL1 and established a gastric cancer cell model with stable knockdown of TTLL1.

[0035] Example 3: Effect of TTLL1 inhibitors on the proliferation of gastric cancer cells 1. Cell cloning experiments The shTTLL1 and shNC cell lines from Example 2 were digested to prepare single-cell suspensions, and the cells were counted. Cells were seeded at a density of 500 cells / well in 6-well plates, with 3 replicates per group. The plates were incubated statically at 37°C with 5% CO2, and the culture medium was changed every 3–4 days. Culture was terminated after approximately 10–14 days when cell colonies were visibly formed. The culture medium was discarded, and the cells were washed with PBS, fixed with 4% paraformaldehyde for 15 minutes, and stained with 0.1% crystal violet solution for 20 minutes. Residual staining was slowly washed away with running water, and the cells were air-dried at room temperature. Cells were scanned and photographed, and the number of cell colonies larger than 50 μm in diameter was counted.

[0036] Staining results as follows Figure 4 As shown, the number of cell clones in the shTTLL1 group was significantly lower than that in the shNC group, indicating that the TTLL1 inhibitor can significantly inhibit the clonal proliferation of gastric cancer cells.

[0037] 2. CCK-8 Experiment shNC and shTTLL1 cells from Example 2 were cultured until they reached the logarithmic growth phase and seeded into 96-well plates at a density of 3000 cells per well, with 5 replicates per group. At 24 h, 48 h, and 72 h post-seeding, 10 μL of CCK-8 reagent (Biosharp) was added to each well, and the plates were incubated at 37°C for 2 h. The absorbance (OD value) of each well was measured using a microplate reader at 450 nm. Cell proliferation curves were plotted with time on the x-axis and OD value on the y-axis.

[0038] Cell proliferation curve as shown Figure 5 As shown, at the 72-hour time point, the optical density OD value of the shTTLL1 group was significantly lower than that of the shNC group (P<0.001), indicating that the TTLL1 inhibitor significantly inhibited the proliferation of gastric cancer cells.

[0039] Example 4: Effect of TTLL1 inhibitors on the migration ability of gastric cancer cells The shTTLL1 and shNC cells from Example 2 were seeded into 6-well plates and cultured until cell confluence reached over 90%. Using a 200 μL sterile pipette tip, three straight scratches were made perpendicular to the bottom of each well in the monolayer. The cells were washed 2-3 times with PBS to remove cell debris. Serum-free medium was then used to inhibit cell proliferation. The scratches at 0 h were photographed and marked under a microscope (100x). After culturing the plates for another 48 h, the same locations were photographed again. The width of the scratches was measured using ImageJ software, and the scratch healing rate was calculated using the following formula: Healing rate (%) = [(0 h scratch width - 48 h scratch width) / 0 h scratch width] × 100% Experimental results and migration rate comparison charts showing the effect of TTLL1 inhibitors on the migration ability of gastric cancer cells, as shown in the figure. Figure 6 As shown, after 48 h of culture, the scratch healing rate of the shTTLL1 group was significantly lower than that of the shNC group (P<0.01), indicating that the TTLL1 inhibitor can significantly inhibit the in vitro migration ability of gastric cancer cells.

[0040] Example 5: Injectable form of TTLL1 inhibitor Take 1 mL of the TTLL1 inhibitor (titer ≥ 1 × 10⁸ IFU / mL) prepared in Example 2, add PBS buffer (pH = 7.4) containing 5% sucrose and 1% human serum albumin to 10 mL, filter aseptically through a 0.22 μm microporous membrane, dispense into vials, and freeze to obtain the TTLL1 inhibitor injection.

[0041] Example 6: Lyophilized powder injection of TTLL1 inhibitor Take the TTLL1 inhibitor injection from Example 5, dispense 1 mL per vial, place in a freeze dryer, pre-freeze, dry once, dry twice, and then cap and seal to obtain the lyophilized powder injection of the TTLL1 inhibitor. Reconstitute with physiological saline before use.

[0042] Example 7: Lipid nanoparticle (LNP) formulation of TTLL1 inhibitor The shRNA targeting TTLL1 with nucleotide sequences as shown in SEQ ID NO: 1 and SEQ ID NO: 2 in Example 2 was used as a TTLL1 inhibitor. It was mixed with ionizable lipids, phospholipids, cholesterol and PEG-lipids, and LNP formulations loaded with TTLL1 inhibitors were prepared by microfluidic technology. It can be used for intravenous injection to improve in vivo delivery efficiency.

[0043] SEQ ID NO:1 shRNA positive strand GTTTGTGTCTCAATCTAATAAttcaagagaTTATTAGATTGAGACACAAAC; SEQ ID NO:2 shRNA antisense strand CAAACACAGAGTTAGATTATTaagttctctAATAATCTAACTCTGTGTTTG.

[0044] Nucleotide sequence of SEQ ID NO:3 TTLL1 The amino acid sequence of SEQ ID NO:4 TTLL1 MAGKVKWVTDIEKSVLINNFEKRGWVQVTENEDWNFYWMSVQTIRNVFSVEAGYRLSDDQIVNHFPNHYELTRKDLMVKNIKRYRKELEKEGSPLAEKDENGKYL YLDFVPVTYMLPADYNLFVEEFRKSPSSTWIMKPCGKAQGKGIFLINKLSQIKKWSRDSKTSSFVSQSNKEAYVISLYINNPLLIGGRKFDLRLYVLVSTYRPLRC YMYKLGFCRFCTVKYTPSTSELDNMFVHLTNVAIQKHGEDYNHIHGGKWTVSNLRLYLESTRGKEVTSKLFDEIHWIIVQSLKAVAPVMNNDKHCFECYGYDIIID DKLKPWLIEVNASPSLTSSTANDRILKYNLINDTLNIAVPNGEIPDCKWNNKSPPKEVLGNYEILYDEELAQGDGADRELRSRQGQSLGPRAGRSRDSGRAVLTTWK The above description is merely a preferred embodiment of the present invention, and should not be construed as limiting the scope of the invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the present invention, and these improvements and modifications are also considered to be within the scope of protection of the present invention.

Claims

1. The application of TTLL1 expression inhibitors in the preparation of drugs for alleviating and / or treating gastric cancer, characterized in that, The TTLL1 expression inhibitor is shRNA; the nucleotide sequence of the shRNA is shown in SEQ ID NO: 1 and SEQ ID NO:

2.

2. The use of a drug containing a TTLL1 expression inhibitor in the preparation of a drug for alleviating and / or treating gastric cancer, characterized in that, The TTLL1 expression inhibitor is a lentivirus comprising shRNA, the nucleotide sequence of which is shown in SEQ ID NO: 1 and SEQ ID NO:

2.

3. The application according to claim 2, characterized in that, The drug also includes pharmaceutically acceptable excipients; the drug is in the form of an injection.

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