苦参碱对肿瘤细胞获得性多药耐药的逆转作用

Reversal effect of matrine on acguired multi-drug resistance in mice tumour cell

目的观察苦参碱对模拟临床化疗CFP方案诱导的小鼠S180肿瘤细胞获得性多药耐药的逆转作用,明确其对多药耐药逆转的作用及其作用机制。以指导临床应用苦参碱逆转肿瘤患者多药耐药,提高化疗疗效。方法模拟临床CFP方案,分别给予小鼠顺铂3mg·kg-1,ip,每周1次;环磷酰胺和5FU各3mg·kg-1,ig,qd,连续4周,流式细胞术荧光检测观察其对MDR细胞膜糖粘蛋白P170、细胞凋亡及其相关因子Fas、Trail和细胞黏附因子CD54的影响。结果苦参碱抑制P170表达、增加对细胞凋亡因子Fas、Trail表达率,促进耐药S180细胞的凋亡,降低细胞黏附因子CD54的表达。结论说明苦参碱逆转肿瘤获得性多药耐药与对肿瘤多种相关生物分子因子的调节有关。临床可以根据肿瘤多药耐药的性质,通过调节多药耐药相关因子逆转肿瘤化疗耐药性,提高临床化疗疗效。

OBJIECTIVE To the reversal effect of matrine on acguired multi-drug resistance in mice S180 tumour cells induced by chemotherapy protocol of CFP. And to discuss the molecular mechanism of action for the use of TCM in clinic to restrain the drugresistant of chemotherapy,thereby improve the curative effect of matrine. METHODS By using the methods of less dosage of chemotherapy CFP, give the mouse cisplatin 3mg·kg^-1 , ip, once a week; cytoxan （CTX） and 5-FU 3 mg·kg^-1 ,ig 4 weeks, set up the mouse models of multi-drug resistance of S180 tumour ceils, and then observe the P170, Fas,CD54 and apoptosis by flow cytometry. RESULTS Matrine could obviously increase the ratio of the express of Fas and the apoptosis of drug resistant tumour cells. And at the same time it could obviously reduce the express of intercellular adhesion molecule（CD54）. CONCLUSION Matrine,with its adjustment of correlated biotic active factors,can intervene the occurrence of the multi-drug resistance of tumor cells induced by chemotherapy.