奥沙利铂不同浓度和时间对诱导大肠癌细胞系SW480耐药效果的影响  

Effects of different concentrations and time of Oxaliplatin for induced colorectal cancer cell line SW480 resistance

作　　者：李彩丽[1] 徐倩倩[1] 孙泽群[1] 卢光新[1] 

机构地区：[1]湖北医药学院附属十堰市人民医院食管肿瘤研究所,湖北十堰442000

出　　处：《胃肠病学和肝病学杂志》2016年第2期134-138,共5页Chinese Journal of Gastroenterology and Hepatology

基　　金：湖北省教育厅科研计划支持(B20122425)

摘　　要：目的采取两种方式体外诱导大肠癌耐奥沙利铂耐药细胞系,比较其耐药机制。方法分别采用低浓度长时间诱导法和高浓度短时间诱导法诱导大肠癌细胞系SW480,建立大肠癌奥沙利铂(Oxaliplatin,OXP)耐药细胞系SW480/OXP1和SW480/OXP2。CCK8法检测SW480、SW480/OXP1和SW480/OXP2耐药指数,绘制细胞生长曲线,检测细胞周期分布;罗丹明123检测细胞膜泵功能,Western blotting检测P-gp和E-cadherin水平。结果 SW480/OXP1对OXP、5-氟尿、顺铂耐药指数分别为10.34±0.35、3.32±0.52、2.76±0.26,SW480/OXP2对OXP、5-氟尿、顺铂耐药指数分别为7.89±0.62、2.78±0.37、2.1±0.23;SW480、SW480/OXP1和SW480/OXP2的群体倍增时间分别为30.50 h、36.64 h和35.87 h。SW480/OXP1和SW480/OXP2的G0/G1比率较亲本细胞上升,而S期比率较亲本细胞下降;正常SW480的罗丹明123排出明显缓于SW480/OXP1和SW480/OXP2。SW480/OXP1和SW480/OXP2的P-gp表达较SW480升高,且SW480/OXP1高于SW480/OXP2。SW480/OXP1和SW480/OXP2的E-cadherin表达均低于SW480,且SW480/OXP2低于SW480/OXP1。结论 OXP低浓度长时间诱导法和高浓度短时间诱导法都可使SW480产生多药耐药性,但是它们的特性仍有部分差异,应按照需要选择合适的诱导方式。Objective To induce the Oxaliplatin （OXP） resistant colorectal cancer cell lines by two different methods, and compare their characteristics and analyze the mechanisms. Methods Two resistant cell lines were established： SW480/OXP1 and SW480/OXP2. They were induced from colorectal cancer cell line SW480 by exposing them to OXP with low concentration and long time or high concentration and short time respectively, and gradually increasing dose of OXP. The cell growth curve and the doubling time were determined by cell counting. The ehemosensitivities of SW480, SW480/OXP1 and SW480/OXP2 to OXP, Cisplatin, and 5-fluorouracil were tested and ICs0 was measured by CCK8. The cell cycle was examined by flow cytometry. The function of P-gp was determined by Rhodamine 123, the ex- pressions of P-gp and E-cadherin were determined by Western blotting. Results The resistance indexes to OXP, 5-flu- orouracil and Cisplatin of SW480/OXP1 were 10.34 ±0.35, 3.32 ± 0.52,2.76 ± 0.26, respectively. The resistance indexes to OXP, 5-fluorouracil and Cisplatin of SW480/OXP2 were 2 7.89±0.62, 2.78 ±0.37, 2.1 ± 0.23, respec- tively. The population double time of SW480, SWdS0/OXP1 and SW480/OXP2 were 30.50 h, 36.64 h and 35.87 h. The number of the SW480/OXP1 and SW480/OXP2 cells exhibiting G0/G1 phase increased and the S phase decreased than SW480 cells. The fluorescence effluence of Rhodamine 123 for SW480/OXP1 and SW480/OXP2 was faster than SW480. The P-gp expression of SW480/OXP1 and SW480/OXP2 was higher than SW480, and the SW480/OXP1 was higher than SW480/OXP2. The E-cadherin expression of SW480/OXP1 and SW480/OXP2 was lower than SW480, and the SW480/OXP2 was lower than SW480/OXP1. Conclusion The two methods can induce multidrug-resistant eolorectal cancer cell lines, but their characteristics are partially different.

关 键 词：大肠癌 耐药 奥沙利铂 

分 类 号：R735.34[医药卫生—肿瘤]