粉防己碱对人口腔上皮癌多药耐药KB-MRP1细胞株多药耐药性的逆转作用

背景与目的:粉防己碱(tetrandrine,Tet)是从中草药粉防已的根块中提取的双苄基异喹啉生物碱,具有逆转P-糖蛋白(P-glycoprotein,P-gp)介导的肿瘤多药耐药(multidrug resistance,MDR)作用.本研究探讨粉防己碱对人口腔上皮癌多药耐药细胞株KB-MRP1耐药的逆转作用及其可能的机制.方法:采用MTT法检测不同浓度粉防己碱对KB-3-1细胞和KB-MRP1细胞的增殖抑制效应;MTT法检测顺铂(cisplatin,DDP)、长春新碱(vincristine,VCR)、阿霉素(adriamycin,ADM)、依托泊苷(etoposide,VP-16)对KB-3-1、KB-MRP1细胞增殖的抑制作用及加用粉防己碱时的变化;采用流式细胞仪检测细胞内ADM蓄积程度以及细胞凋亡.结果:1.5μg/ml及更低浓度的粉防己碱对KB-3-1和KB-MRP1细胞无明显细胞毒性作用.KB-MRP1对VCR、ADM、VP-16和DDP的耐药倍数分别为21.23、38.39、12.47和1.31.加入1 μg/ml粉防己碱后,KB-MRP1对VCR、ADM、VP-16的耐药逆转倍数分别为4.96、5.85和4.27倍.加入1.5 μg/ml粉防己碱后,KB-MRP1对上述化疗药物的敏感程度提高更明显.1.5 μg/ml浓度的粉防己碱可明显提高ADM在KB-MRP1细胞内的蓄积,增强VCR诱导的KB-MRP1细胞凋亡.结论:粉防己碱可以逆转KB-MRP1细胞的多药耐药,逆转效果与药物浓度有关,逆转机制可能与增加细胞内化疗药物蓄积和增强化疗药物诱导的细胞凋亡有关.

Reversing multidrug resistance of epidermoid carcinoma drug-resistant cell line KB-MRP1 by tetrandrine

BACKGROUND & OBJECTIVE: Tetrandrine (Tet), a bisbenzylisoquinoline albaloid isolated from the Chinese herb "Hanfangji" (Radix Stephania Tetrandra), could effectively reverse P-glycoprotein-mediated multidrug resistance. This study was to investigate the reversal effect of tetrandrine on multidrug resistance of human epidermoid carcinoma cell line KB-MRP1. METHODS: The effects of tetrandrine on the proliferation of KB-3-1 and KB-MRP1 cells were observed by MTT assay. The inhibitory effects of cisplatin (DDP), vincristine (VCR), adriamycin (ADM) and etoposide (VP-16) used alone or in combination with tetrandrine on the proliferation of KB-3-1 and KB-MRP1 cells were evaluated by MTT assay. The effects of tetrandrine on ADM accmulation in KB-MRP1 cells and VCR-induced apoptosis were determined by flow cytometry (FCM). RESULTS: Tetrandrine at the concentration of 1.5 microg/ml and below showed no significant cytotoxicity to KB-3-1 and KB-MRP1 cells. The resistance of KB-MRP1 cells to VCR, ADM, VP-16 and DDP were 21.23, 38.39, 12.47 and 1.31 folds of that of KB-3-1 cells. When added 1 microg/ml tetrandrine, the chemosensitivity of KB-MRP1 cells to VCR, ADM and VP-16 were increased to 4.96, 5.85 and 4.24 folds, respectively; when added 1.5 microg/ml tetrandrine, the chemosensitivity of KB-MRP1 cells to VCR, ADM and VP-16 were much higher. When treated with 1.5 microg/ml tetrandrine, ADM accumulation in KB-MRP1 cells and the VCR-induced apoptosis were enhanced significantly. CONCLUSION: Tetrandrine could moderately reverse the multidrug resistance of KB-MRP1 cells through increasing the accumulation of chemo-drugs in cells and promoting apoptosis.