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- Title
IGFBP3 基因启动子高甲基化所致表达下降促进胃癌化疗耐药.
- Authors
刘立宇; 刘霆; 陈柏林; 李佳; 李康
- Abstract
Objective: To study the expression of insulin-like growth factor binding protein 3(IGFBP3) in chemosensitivity and chemosensitivity cells and tissues of gastric cancer, and to explore its function and mechanism of abnormal expression in the chemoresistance of gastric cancer. Methods: The expression of IGFBP3 in chemotherapeutic drug-sensitive gastric cancer cells AZ521 and SC-M1, expressions of cisplatin-resistant cells AZ521/cisplatin, SC-M1/cisplatin and gastric cancer were detected by real-time quantitative fluorescence polymerase chain reaction(qRT-PCR) and Western blot assay(WB). After decreasing and increasing the expression of IGFBP3, the sensitivity of gastric cancer cells to chemotherapeutic drugs was detected by cell counting kit-8(CCK-8)reagent and flow cytometry(FCM). The promoter methylation level of IGFBP3 was determined by the methylation specific PCR(MSP)assay. Results: The expression of IGFBP3 in chemo-tolerant gastric cancer cells and tissues was lower than that in chemo-sensitive gastric cancer cells and tissues(P <0.05). Interference of IGFBP3 expression in sensitive cells can promote drug resistance of gastric cancer cells. While recovery of IGFBP3 expression in drug-resistant cells can significantly reversed drug resistance. MSP results showed that the expression of IGFBP3 was regulated by DNA methylation. Higher methylation of IGFBP3 promoter in drug-resistant cells resulted in decreased expression of IGFBP3(P <0.05). The drug-resistant gastric cancer cells were treatment with methyltransferase inhibitor dicetabine(DAC), the expression of IGFBP3 was restored, its sensitivity to chemotherapeutic drugs were increased(P<0.05).Conclusion: DNA hypermethylation in the promoter region of IGFBP3 leads to a decrease in its expression, which leads to a decrease in the ability of chemotherapeutic drugs to induce apoptosis of gastric cancer cells, and ultimately leads to chemotherapeutic resistance of gastric cancer cells.
- Publication
Progress in Modern Biomedicine, 2019, Vol 19, Issue 8, p1441
- ISSN
1673-6273
- Publication type
Article
- DOI
10.13241/j.cnki.pmb.2019.08.009