参芪扶正注射液对胰腺癌多药耐药逆转作用研究  

Reversal Effect of Shengqi Fuzheng Injection on Pancreatic Cancer Multidrug Resistance Cells

作　　者：文柳静[1] 王晨[1] 任丽[1] 

机构地区：[1]天津医科大学肿瘤医院国家肿瘤临床医学研究中心天津市肿瘤防治重点实验室天津市恶性肿瘤临床医学研究中心,天津300060

出　　处：《中国药学杂志》2017年第13期1147-1151,共5页Chinese Pharmaceutical Journal

基　　金：天津市中医中西医结合科研课题(2015063)

摘　　要：目的探讨参芪扶正注射液(SQFZ)对胰腺癌多药耐药的逆转作用及初步分子机制。方法以胰腺癌细胞株Patu8988为研究对象,采用氟尿嘧啶(5-Fu)诱导得到Patu8988/5-Fu耐药细胞株;采用四甲偶氮唑蓝(MTT)法测定Patu8988/5-Fu耐药倍数、SQFZ的细胞增殖抑制作用以及SQFZ对Patu8988/5-Fu耐药细胞株的逆转倍数;采用流式细胞分析技术(FCM)测定SQFZ对细胞内罗丹明123(Rho123)蓄积的影响;采用实时定量PCR技术检测SQFZ对耐药细胞株MDR1、Bcl-2和Bax基因表达的调控作用;采用蛋白质免疫印迹(Western Blot)技术检测SQFZ对耐药细胞株Bcl-2、Bax和P-gp蛋白表达情况影响。结果浓度为5、10和20μL·m L^(-1)的SQFZ可逆转Patu8988/5-Fu细胞的耐药性,逆转倍数依次为1.5、2.3和3.4倍。SQFZ剂量依赖性地增加Patu8988/5-Fu细胞的Rho123蓄积量(r=0.979,P<0.05)。分子机制研究表明,SQFZ下调Patu8988/5-Fu细胞MDR1和Bcl-2的基因表达,上调Bax基因表达。SQFZ可使Patu8988/5-Fu细胞中P-gp和Bcl-2的蛋白表达水平下降,使Bax蛋白表达水平上升。结论 SQFZ具有逆转Patu8988/5-Fu细胞多药耐药的作用,其作用机制可能与MDRl、Bcl-2和Bax基因的转录及蛋白表达有关。OBJECTIVE To explore the reversal effect and molecular mechanism of shengqi fuzheng injection （SQFZ） on pancreatic cancer muhidrug resistance（MDR） ceils. METHODS Patu8988 was exposured to fluorouracil（5-Fu） to obtain stable 5-Fu-resistant Patu8988/5-Fu cell lines. MTT assay was used to detect the inhibition of SQFZ on cell proliferation and the resistance index of Patu8988/5-Fu and reversal index of SQFZ were calculated. Flow cytometry （FCM） was employed to measure the accumulation of Rho123 in cells. The mRNA expression of MDR1, Bcl-2 and Bax and presence of Bcl-2, Bax and P-gp protein were analyzed by quantitative real-time PCR and Western blot methods respectively. RESULTS SQFZ at the concentration of 5,10,20 μL·mL^-1 obviously reversed MDR of Patu8988/5-Fu cells, with the reversal index of 1.5,2. 3 and 3.4 respectively. It increased Rho123 accumulation in a dose-dependent manner in MDR cells（r = 0. 979, P 〈 0. 05）. The study revealed that SQFZ downregulated the expressions of MDR1 and Bcl2 gene and upregulated the expression of Bax gene. Furthermore, SQFZ decreased the expression of P-gp and Bcl-2 protein, and increased the expression of Bax protein in Patu8988/5-Fu cells. CONCLUSION SQFZ can reverse multidrug resistance of Patu8988/FU cells, likely by modulating gene transcription and protein expression of MDR1, Bcl-2 and Bax.

关 键 词：胰腺癌 多药耐药 参芪扶正注射液 Patu8988/5-Fu 

分 类 号：R965[医药卫生—药理学]