CN-122005598-A - Application of IGFBP7 in preparation of stomach adenocarcinoma treatment drug

Abstract

The invention belongs to the technical field of medical biology, and particularly relates to application of IGFBP7 in preparation of stomach adenocarcinoma treatment drugs. The invention screens IGFBP7 closely related to gastric adenocarcinoma by various bioinformatics technologies as a molecular marker, detects the expression of IGFBP7 in gastric adenocarcinoma by immunohistochemistry and establishes a scoring system with combined staining intensity and positive cell proportion to evaluate the prognosis of patients. Experimental results show that IGFBP7 knockdown can effectively inhibit proliferation and migration of gastric adenocarcinoma cells, induce apoptosis and induce S-phase retardation. Further experiments on gastric adenocarcinoma cells and monocytes show that IGFBP7 promotes polarization of M2 type macrophages in the immune microenvironment of gastric adenocarcinoma tumors.

Inventors

• LIU JIAHAO
• CUI HONGXIA
• WANG ZHIMING

Assignees

• 核工业总医院

Dates

Publication Date

20260512

Application Date

20260409

Claims (8)

1. 1. The application of the sequence of siRNA of specific targeting IGFBP7 gene shown as SEQ ID No.2 or SEQ ID No.3 in preparing gastric adenocarcinoma therapeutic drug.
2. 2. The use of claim 1, wherein the medicament inhibits tumor growth by inhibiting IGFBP7 expression.
3. 3. The use of claim 1, wherein the medicament inhibits gastric adenocarcinoma cell proliferation and induces apoptosis by inhibiting IGFBP7 expression.
4. 4. The use of claim 1, wherein the medicament induces S-phase arrest in tumor cells by inhibiting IGFBP7 expression.
5. 5. The use of claim 1, wherein the medicament inhibits tumor-associated M2-type macrophage polarization by inhibiting IGFBP7 expression.
6. 6. The sequence of siRNA of specific targeting IGFBP7 gene shown as SEQ ID No.2 or SEQ ID No.3 is applied to preparing gastric adenocarcinoma detection kit.
7. 7. The use according to claim 6, wherein the kit further comprises a rabbit-derived polyclonal anti-IGFBP 7 antibody, HRP-labeled goat anti-rabbit secondary antibody, and DAB chromogenic reagent.
8. 8. A drug for treating gastric adenocarcinoma, which is characterized in that the drug contains a sequence of siRNA specifically targeting IGFBP7 gene as shown in SEQ ID No.2 or SEQ ID No. 3.

Description

Application of IGFBP7 in preparation of stomach adenocarcinoma treatment drug Technical Field The invention belongs to the technical field of medical biology, and particularly relates to application of IGFBP7 in preparation of stomach adenocarcinoma treatment drugs. Background Gastric adenocarcinoma is one of the common malignant tumors of the digestive system, and the incidence and death rate of the malignant tumor in the death cause of the malignant tumor are high. Although the diagnosis and treatment means such as operation, radiotherapy and chemotherapy are continuously advanced, the overall prognosis of patients with gastric adenocarcinoma is still not ideal, and the recurrence and metastasis rate are high. Therefore, it is of great clinical importance to find novel molecular markers that can be used to assess patient prognosis and guide treatment. IGFBP7 is a low affinity Insulin-like growth factor (Insulin-like growth factor, IGF) conjugate and IGFBP7 is expressed in both epithelial and meta She Yuanxing tumors. Studies have shown that IGFBP7 plays an important role in the development and progression of malignant melanoma, glioma, thyroid cancer and other tumors. However, the studies of the expression pattern and prognostic impact in gastric adenocarcinoma are still in the initiation phase, and the mechanism of action of gastric adenocarcinoma in particular has not been systematically elucidated. Disclosure of Invention Aiming at the problems and the defects existing in the prior art, the invention aims to provide the application of IGFBP7 in preparing gastric adenocarcinoma therapeutic drugs, and the IGFBP7 inhibition strategy provided by the invention has a better effect in gastric adenocarcinoma therapy, thereby providing a new direction for prognosis evaluation of gastric adenocarcinoma and immune-related targeted drug development. The invention is realized by the following technical scheme: the application of the sequence of siRNA of specific targeting IGFBP7 gene shown as SEQ ID No.2 or SEQ ID No.3 in preparing gastric adenocarcinoma therapeutic drug. The amino acid sequence of IGFBP7 is: MERPSLRALLLGAAGLLLLLLPLSSSSSSDTCGPCEPASCPPLPPLGCLLGETRDACGCCPMCARGEGEPCGGGGAGRGYCAPGMECVKSRKRRKGKAGAAAGGPGVSGVCVCKSRYPVCGSDGTTYPSGCQLRAASQRAESRGEKAITQVSKGTCEQGPSIVTPPKDIWNVTGAQVYLSCEVIGIPTPVLIWNKVKRGHYGVQRTELLPGDRDNLAIQTRGGPEKHEVTGWVLVSPLSKEDAGEYECHASNSQGQASASAKITVVDALHEIPVKKGEGAEL（SEQ ID No.1）. siIGFBP7-1:(5′-3′)UGGUAUCUCCUCUAAGUAATT(SEQ ID No.2); siIGFBP7-2:(5′-3′)CGAGCAAGGUCCUUCCAUATT(SEQ ID No.3)。 Further, the agents inhibit tumor growth by inhibiting IGFBP7 expression. Further, the agents inhibit proliferation and migration of gastric adenocarcinoma tumors by inhibiting IGFBP7 expression. Further, the agents elicit S-phase arrest in tumor cells by inhibiting IGFBP7 expression. Further, the agent inhibits tumor-associated M2-type macrophage polarization by inhibiting IGFBP7 expression. The invention also provides application of the sequence of siRNA of the specific targeting IGFBP7 gene shown as SEQ ID No.2 or SEQ ID No.3 in preparing a gastric adenocarcinoma detection kit. Further, the kit also comprises a rabbit polyclonal anti-IGFBP 7 antibody, an HRP-labeled goat anti-rabbit secondary antibody and a DAB chromogenic reagent. The invention also provides a medicine for treating gastric adenocarcinoma, which contains a sequence of siRNA of a specific targeting IGFBP7 gene as shown in SEQ ID No.2 or SEQ ID No. 3. The beneficial effects are that: (1) The protein-IGFBP 7 closely related to prognosis of gastric adenocarcinoma is screened out by combining multiple bioinformatics means, and the expression condition of the IGFBP7 in tumor tissues of 93 gastric adenocarcinoma patients is detected by immunohistochemistry, so that the high expression of the IGFBP7 in the gastric adenocarcinoma tissues is found, and the expression level is obviously related to the prognosis of the patients. The prognosis of patients with high IGFBP7 expression is significantly worse than that of patients with low IGFBP7 expression, indicating potential prognostic value. IGFBP7 can be used as a novel prognostic marker by establishing scoring criteria by immunohistochemical IHC. (2) In vitro cell experiments prove that the knockdown IGFBP7 expression can effectively inhibit proliferation and migration of gastric adenocarcinoma cells, induce apoptosis and block cell cycle in S phase. This reveals the potential of IGFBP7 as a therapeutic target, inhibiting its expression may directly produce an anti-tumor effect. (3) According to the invention, through a co-culture experiment, IGFBP7 can promote the polarization of tumor-associated macrophages to M2 type, which indicates that IGFBP7 participates in the regulation of tumor immune microenvironment. Thus, inhibition of IGFBP7 expression not only directly inhibits tumor cells, but may also exert synergistic antitumor effects by remodelling the immune microenvironment (inhibiting M2 polarizat