Cheeloo College of Medicine, Shandong University, Jinan, China.
Eur Rev Med Pharmacol Sci. 2020 Jul;24(14):7753-7763. doi: 10.26355/eurrev_202007_22278.
Gastric carcinoma is one of the most common malignant tumors and one of the most common cancer-related fatal diseases. Chemotherapy is considered as the major therapy for advanced gastric cancer, and the curative effect of chemotherapy directly affects the treatment of advanced gastric cancer. Drug resistance of tumor cells is one of the important causes that induces failure of chemotherapy. Previous studies have demonstrated that verapamil (VER) can reverse drug resistance by inhibiting the P-glycoprotein (P-gp), which is one of the main targets of VER. The present study aimed at investigating the function of glucosylceramide synthase (GCS) in the VER-induced reversal of doxorubicin (ADM) chemotherapy resistance in gastric carcinoma.
In the current study, the 4 GC cell line was selected for investigation. The IC50 values of gastric cancer cells were measured using CCK-8 assay. The expression levels of candidate genes in gastric carcinoma cells were measured by RT-qPCR. The expression levels of candidate protein in gastric carcinoma cells were measured by Western blot. The expression of GCS protein in clinical specimens of GC receiving VER+TACE therapy was measured by immunohistochemistry. The test of gastric carcinoma cell apoptosis was measured by Annexin V-FITC/PI double-staining.
We found that the expression levels changes of the GCS gene can influence the effects of ADM+VER on cell apoptosis. The role and mechanism of GCS gene in reversing the chemotherapy resistance of gastric carcinoma cells to ADM were explored.
In future research, we will explore the mechanism of how GCS affects drug resistance in gastric carcinoma and related signal transduction pathway.
胃癌是最常见的恶性肿瘤之一，也是癌症相关死亡的最常见原因之一。化疗被认为是治疗晚期胃癌的主要方法，化疗的疗效直接影响晚期胃癌的治疗效果。肿瘤细胞的耐药性是导致化疗失败的重要原因之一。先前的研究表明，维拉帕米（VER）可以通过抑制 P 糖蛋白（P-gp）来逆转耐药性，P-gp 是 VER 的主要靶点之一。本研究旨在探讨葡萄糖神经酰胺合酶（GCS）在 VER 诱导的胃癌多柔比星（ADM）化疗耐药逆转中的作用。
本研究选择了 4 个 GC 细胞系进行研究。用 CCK-8 法测定胃癌细胞的 IC50 值。用 RT-qPCR 测定候选基因在胃癌细胞中的表达水平。用 Western blot 测定候选蛋白在胃癌细胞中的表达水平。用免疫组化法测定接受 VER+TACE 治疗的 GC 临床标本中 GCS 蛋白的表达。用 Annexin V-FITC/PI 双染法检测胃癌细胞凋亡试验。
我们发现 GCS 基因表达水平的变化可以影响 ADM+VER 对细胞凋亡的影响。探讨了 GCS 基因在逆转胃癌细胞对 ADM 化疗耐药中的作用及其机制。
在未来的研究中，我们将探讨 GCS 如何影响胃癌的耐药性以及相关信号转导通路的机制。
