多药耐药相关基因及其蛋白在介导胰腺癌细胞原发性耐药中的作用及调控  

Significance and reversal of MDR1/P-gp in pancreatic cancer chemotherapy

作　　者：郭俊超[1] 赵玉沛[1] 廖泉[1] 朱预[1] 

机构地区：[1]中国医学科学院中国协和医科大学 北京协和医院基本外科,100730

出　　处：《中华外科杂志》2007年第21期1488-1490,共3页Chinese Journal of Surgery

基　　金：国家自然科学基金(30371389)

摘　　要：目的检测多药耐药相关基因(MDR1)及其蛋白(P-gp)在胰腺癌细胞株的表达,初步探讨胰腺癌发生先天性耐药的机理。方法选择8株人胰腺癌细胞株,采用 RT-PCR 方法检测 MDR1mRNA 在胰腺癌细胞中的表达;通过免疫细胞化学方法检测 P-gp 的表达;以流式细胞仪检测胰腺癌细胞对罗丹明的外排情况,评价 P-gp 泵功能;最后通过 P-gp 抑制物维拉帕米与化疗药物联合应用,检测其对胰腺癌细胞的杀伤作用。结果 MDR1 mRNA 在胰腺癌细胞株 SW1990中的表达最高,除PCT-2未检测到 MDR1的表达外,其余6株细胞均有 MDR1的微弱表达;免疫细胞化学染色结果证实P-gp 在 SW1990中的表达明显高于其他细胞株。57.9%±5.4%的 SW1990细胞内有罗丹明蓄积,而在 P-gp 阴性对照细胞中,99.5%±3.3%的细胞内存在罗丹明的积聚,两者差异有统计学意义(P<0.05)。P-gp 抑制物维拉帕米与阿霉素或表阿霉素联合应用时可以部分逆转肿瘤细胞对化疗药物的耐药性。结论 MDR1及 P-gp 在人胰腺癌细胞中存在一定量的表达;维拉帕米联合阿霉素可以明显抑制 P-gn 阳性细胞的生长。Objective To delineate the mechanism of primary drug resistance in pancreatic cancer cell lines by investigating mutidrug resistant gene 1 and its protein （P-gp）. Methods Reverse transcription PCR （RT-PCR） and immunocytochemistry （ICC） were carried out to investigate the expression of the MDR1 and P-gp in 8 pancreatic cancer cell lines. Flow cytometry was performed to detect P-gp function in SW1990 and HL60 cell lines. In addition, verapamil, combined with chemotherapeutic agents was carried out to evaluate its potential effect in pancreatic cancer cells. Results The highest expression level of MDR1 mRNA was proven in SW1990 cell line by RT-PCR,while the absent expression was found in PCT-2. Weak MDR1 mRNA expression were found in PCT-3, PCT-4,ASPC,Cap-1, Mia-PaCa-2 and Pane-1 cell lines. ICC showed that P-gp was localized mainly in the membrane and partly in the plasma. P-gp overexpression was also present in SW1990. The accumulation of Rhodamin123 in SW1990 was significantly decreased （57. 9%± 5.4% ） compared with its expression in HL60 （ 99. 5% ± 3.3% ） （ P 〈 0. 05 ）. Verapamil （ VPM ）, combined with ADM or E-ADM showed a potential effect on reversing drug resistance mediated by P-tip in pancreatic cancer chemotherapy. Conclusions MDR1 and its protein P-tip are indeed expressed in some extent in pancreatic cancer cell lines. VPM combined with ADM might imply a new strategy in pancreatic cancer chemotherapy.

关 键 词：胰腺肿瘤 药物疗法 抗药性 多药 

分 类 号：R735.9[医药卫生—肿瘤]