胰腺癌组织和细胞的耐药性与ABC转运蛋白基因1 的关系

摘要] 目的：探讨胰腺癌耐药性与ABC转运蛋白基因1（ABCB1）的表达及其启动子甲基化的关系。方法：选用2015 年8月至2018 年8 月福建省肿瘤医院病理确诊的15 例胰腺癌及癌旁组织、3 例正常胰腺组织标本以及胰腺癌细胞株SW1990，用间歇浓度梯度倍增法将SW1990 细胞株诱导分化为吉西他滨（GEM）耐药胰腺癌细胞株SW1990/GZ。用qPCR分别检测胰腺癌及癌旁组织和SW1990、SW1990/GZ细胞中ABCB1 表达水平，用MSP-PCR法检测胰腺癌组织和SW1990、SW1990/GZ细胞中ABCB1启动子区域甲基化程度。结果：与SW1990 相比，SW1990/GZ细胞空泡增多、核分裂像增加、呈现团块生长，并呈现更强的耐药性（P<0.05）。胰腺癌组织中ABCB1 表达水平明显高于癌旁组织（P<0.01）。SW1990 和SW1990/GZ细胞中ABCB1 表达水平显著高于正常胰腺组织（P<0.05 或P<0.01），其中SW1990/GZ 细胞中ABCB1 表达水平高于SW1990 细胞（P<0.05）。SW1990 和SW1990/GZ细胞及正常胰腺组织中的ABCB1 启动子均呈低甲基化状态。胰腺癌和正常胰腺组织中甲基化率分别为6.7%（1/15）及0.00%（0/3），差异无统计学意义（均P>0.05）。结论：胰腺癌组织和细胞中ABCB1 表达增高与耐药性有关，但其基因表达不依赖于启动子的甲基化调控。

Relationship between drug resistance and ABCB1 gene in pancreatic cancer

Abstract] Objective: To investigate the relationship between drug resistance and expression of ABC-binding cassette subfamily B member 1 (ABCB1) as well as its promoter methylation in pancreatic cancer. Methods: Fifteen pairs of pancreatic cancerous tissues and corresponding para-cancerous tissues, which were pathologically verified in Fujian Cancer Hospital from August 2015 to August 2018, were collected for this study; in addition, 3 cases of normal pancreatic tissues and pancreatic cancer cell line SW1990 were also collected. Gemcitabine (GEM)-resistant human pancreatic cancer cell line SW1990/GZ was induced by intermittent concentration gradient multiplication method. The expression level of ABCB1 in SW1990 cells, SW1990/GZ cells, pancreatic cancer tissues and apara-cancerous tissues was detected by qPCR. Methylation of ABCB1 promoter region in SW1990 cells, SW1990/GZ cells and pancreatic cancerous tissues was determined by MSP-PCR. Results: Compared with SW1990 cells, the morphology of SW1990/GZ cells showed more vacuoles, more mitotic images, clumpy growth and increased drug resistance (P<0.05). ABCB1 expression in pancreatic cancer tissues was significantly higher than that in para-cancerous tissues (P<0.01). The expression of ABCB1 in SW1990 and SW1990/GZ cells was significantly higher than that in normal pancreatic tissues (P<0.05 or P<0.01), and the expression of ABCB1 in SW1990/GZ cells was higher than that in SW1990 cells (P<0.05). ABCB1 promoters in SW1990, SW1990/GZ cells and normal pancreatic tissues were hypomethylated. Rate of methylation in pancreatic cancerous tissues and normal pancreatic tissues was 6.7%(1/15) and 0.00%(0/3) respectively, and the difference was statistically insignificant (all P>0.05). Conclusion: Increased ABCB1 expression in pancreatic cancer tissues and cells is associated with drug resistance, but its gene expression does not depend on promoter methylation regulation.