溴泰君(W198)联合加温逆转MCF-7/ADM细胞株耐药的实验研究

EXPERIMENTAL STUDY ON THE REVERSAL EFFECT OF HEATING COMBINED WITH 5-BROMOTETRANDRINE(W198)ON MUTI-DRUG RESISTANT OF BREAST CANCER CELL LINE MCF-7/ADM

[目的]观察溴泰君(W198)联合加温对人乳腺癌耐药细胞的耐药逆转作用。[方法]以人乳腺癌细胞MCF-7为对照,以人乳腺癌耐药细胞MCF-7/Adm为研究对象,当阿霉素(Adm)作用浓度为1μg·ml-1时,不同温度加温(37℃～42℃)与不同浓度(0.125μmol·L-1～1.0μmol·L-1)W198联合作用1h条件下,检测MCF-7及MCF-7/Adm的细胞生长抑制率、细胞内Adm的荧光强度、细胞表面P-糖蛋白(p-gp)荧光强度,统计分析其与加温温度和W198浓度间的变化趋势。[结果]MCF-7/Adm细胞对Adm的敏感性明显低于MCF-7细胞。加温联合W198作用于MCF-7/Adm,随加温温度和W198浓度增加,细胞表面P-gp表达降低,细胞内Adm浓度及细胞生长抑制率增加。42℃加温与1.0μmol·L-1W198联合作用时能最大程度的逆转MCF-7/Adm对Adm的耐药。[结论]加温联合W198对于人乳腺癌耐药细胞的耐药逆转具有协同作用。

[Objective] To observe the reversal effect of heating combined with 5-bromotetrandrine （W198） on mutidrug resistant of breast cancer cell line MCF-7/Adm. [ Methods] The breast cancer cell line MCF-7 was included as control, and drug resistant the breast cancer line MCF-7/Adm as participants. At different temperature at the range of 37%-42% and different concentrations of W198 at the range of 0.125μmol/L-1.0μmol/L, the mud-drug resistant breast cancer cell line MCF-7/Adm was treated with 1μg·ml^-1 Adm for one hour. The inhibitory rates of cell growth for MCF-7 and MCF-7/Adm, fluorescence intensity of Adm in cells and cell surface P-glycoprotein （p-gp） were detected, their association of variance tendency with the temperature of heating and concentration of W198 were analyzed. [ Results] The sensitivity of MCF-7/Adm to Adm was significantly lower than that of MCF-7. With the increased temperature of heating and concentration of W198, the inhibitory rate and intracelhdar concentration of Adm of MCF-7/Adm cells increased, while expression of p-gp decreased. 1.0μmol·L^-1 W198 combined with 1μg·ml^-1 Adm at 42℃ could greatly reverse the multi-drug resistance of MCF-7/Adm to the Adm. [Gonclusion] W198 combined with heating showed joint action to the multi-drug resistance of MCF-7/Adm cells.