DBC1在胃癌耐药中的作用和机制初探  

Effects and Mechanism of DBC1 in Drug Resistance Phenotype of Gastric Cancer

作　　者：张永国 邵晓冬 刘婕[2] 林浩 邹德莉 ZHANG Yongguo;SHAO Xiaodong;LIU Jie;LIN Hao;ZOU Deli(Department of Gastroenterology,General Hospital of Northern Theater Command,Shenyang Liaoning110016,China)

机构地区：[1]北部战区总医院消化内科,辽宁沈阳110016 [2]沈阳药科大学药剂实验中心

出　　处：《华南国防医学杂志》2022年第12期943-947,共5页Military Medical Journal of South China

基　　金：辽宁省自然科学基金资助项目(2019-ZD-1058)

摘　　要：目的初步探讨乳腺癌缺失基因1(deleted in breast cancer 1,DBC1)在胃癌耐药中的作用和可能机制。方法选取对化疗敏感和化疗耐药的胃癌患者,利用免疫组织化学染色法检测DBC1表达差异;在SGC7901胃癌细胞系中通过DBC1-shRNA载体下调DBC1的表达,利用四甲基偶氮唑盐(methylthiazolyl tetrazolium,MTT)、流式细胞术观察胃癌细胞对顺铂(cisplatin,CDDP)、5-氟尿嘧啶(5-fluorouracil,5-FU)等化疗药物的敏感性;利用Western blot检测多药耐药基因1(multidrug resistance gene 1,MDR1)、多药耐药相关蛋白(multidrug resistance associated protein,MRP)的表达变化,初步揭示可能的分子机制。结果在化疗耐药的胃癌患者中,DBC1表达明显高于化疗敏感的胃癌患者;在SGC7901胃癌细胞,下调DBC1表达可以提高胃癌细胞对CDDP和5-FU的敏感性、降低半抑制浓度(half maximal inhibitory concentration,IC50)值,增强CDDP等化疗药物对胃癌细胞的杀伤;在SGC7901胃癌细胞中下调DBC1的表达后,MDR1的表达相应下调,而MRP的表达无明显变化。结论DBC1参与胃癌耐药的发生,在胃癌耐药中发挥一定作用,DBC1可作为逆转胃癌耐药的潜在靶点。Objective To investigate the effects and mechanism of deleted in breast cancer 1(DBC1)in drug resistance of gastric cancer.Methods Patients with chemotherapy-sensitive and chemotherapy-resistant gastric cancer were selected,the difference of DBC1 expression was detected by immunohistochemical staining;in SGC7901 gastric cancer cell line,DBC1 expression was down-regulated by DBC1-shRNA vector.The sensitivity of gastric cancer cells on sensitility of cisplatin(CDDP),5-fluorouracil(5-FU)and other chemotherapy drugs were observed by methylthiazolyl tetrazolium(MTT)and flow cytometry.The expression changes of multidrug resistance gene 1(MDR1)and multidrug resistance associated protein(MRP)were detected by Western blot.The possible molecular mechanism was preliminarily revealed.Results In the patients with chemotherapy-resistant gastric cancer,DBC1 expression was significantly higher than that in the patients with chemotherapy-sensitive gastric cancer;in SGC7901 gastric cancer cells,down-regulation of DBC1 expression could improve the sensitivity of gastric cancer cells to CDDP and 5-FU and reduce the value of half maximal inhibitory concentration(IC50),thus enhancing the killing effects of CDDP and other chemotherapy drugs on gastric cancer cells;in SGC7901 gastric cancer cells,the expression of MDR1 was down-regulated after DBC1 expression down-regulated,while the expression of MRP was not significantly changed.Conclusion DBC1 is involved in the occurrence of drug resistance in gastric cancer and plays a certain role in drug resistance in gastric cancer.DBC1 can be used as one of the potential targets to reverse drug resistance in gastric cancer.

关 键 词：乳腺癌缺失基因1 胃癌 耐药 顺铂 5-氟尿嘧啶 SGC7901胃癌细胞 

分 类 号：R735.2[医药卫生—肿瘤]