蛇床子素逆转人膀胱肿瘤T24/ADM细胞耐药作用及其机制  

Reversal effect and mechanism of osthole on the multidrug-resistance of human bladder cancer cells T24/ADM

作　　者：王晓华[1] 张绍谨[1] 郭祥[1] 孙孟良[1] 李沁鹏[1] 刘红耀[2] 

机构地区：[1]山西医科大学,山西太原030001 [2]山西医学科学院山西大医院泌尿外科,山西太原030001

出　　处：《中国当代医药》2012年第7期7-9,共3页China Modern Medicine

摘　　要：目的研究蛇床子素(osthole,OST)对T24/ADM细胞多药耐药的逆转及对P-gp表达、功能的影响。方法采用MTT法筛选OST对T24/ADM细胞无毒或低毒浓度,以筛选出的浓度作为耐药逆转的实验浓度。分别利用MTT法分别检测阿霉素(adriamycin,ADM)、氟尿嘧啶(fluorouracil,FU)及顺铂(cisplatin,DDP)对细胞株T24和T24/ADM以及OST处理后的T24/ADM细胞的半数抑制浓度IC50。用流式细胞仪测定OST对T24/ADM细胞上P-gp表达的影响。结果浓度17μmol/LOST对T24/ADM无明显细胞毒性,T24/ADM对ADM、FU和DDP均有不同程度的。耐药,耐药倍数分别为18.86、5.09、3.28,使用17μmol/LOST处理后T24/ADM对上述ADM、FU和DDP的敏感性均有不同程度的提高,ADM对耐药细胞株的IC50由(0.962±0.017)μg/mL降至(0.364±0.031)μg/mL,逆转指数为2.64;FU对耐药细胞株的IC50由(0.723±0.003)μg/mL降至(0.463±0.021)μg/mL,逆转指数为1.56;DDP对耐药细胞株的IC50由(0.664±0.007)μg/mL降至(0.587±0.016)μg/mL,逆转指数为1.13,使T24/ADM细胞内P-gp蛋白表达明显下降,下降了16.32%(P<0.05)。结论蛇床子素在体外能部分逆转T24/ADM的耐药性,逆转机制可能是通过抑制P-gp蛋白表达实现的。Objective To study the reversal of osthole on the role of drug resistance T24/ADM cells. Methods The low or no cytotoxicity concentration of OST for T24/ADM cells by MTT, and take these concentrations as the experimental con centrations. The inhibition rate of ADM, FU, DDP without and with no cytotoxicity concentration of OST to T24 and T24/ ADM cells were evaluated With MTT assay. The IC50 of different agents was counted. The concentrations of P-gp in T24/ ADM cells with and without OST were measured by flow cytometey（FCM）. Results Osthol at the concentration of 17 μmol/L had no significant cytoxicity to T24/ADM cells. T24/ADM cells were resistant to ADM, FU and DDP and the resistance in dex was 18.86, 5.09, 3.28 respectively. The sensitivity of T24/ADM to ADM, FU and DDP was significantly increased by osthol in the concentration of 20 μmol/L. The inhibitive concentration 50 （IC50） of ADM declined from （0.962±0.017）μg,/mL to （0.364±0.031） μg/mL with a reversion index of 2.64. The IC50 of Fu declined from （0.723±0.003） μg/mL to （0.463± 0.021） μg/mL with a reversion index of 1.56. The IC50 of DDP declined from （0.664±0.007） μg/mL to （0.587±0.016） μg/mL with a reversion index of 1.13. FCM results indicated that the positive expression rate of P-gP dropped （P 〈 0.05）. Con clusion Osthole had the reversal effect on T24/ADM cell resistance, the mechanism of reversion is related with clown regu lation of expression of P-gp.

关 键 词：蛇床子素 T24/ADM细胞:耐药逆转:机制 

分 类 号：R737.1[医药卫生—肿瘤]