逆转人宫颈癌耐药细胞耐药性的实验研究

Experimental study on mitomycin C resistance and its reversion in human cervical cancer

目的 本研究旨在探讨SDZPSC833和维拉帕米 (verapamil,VER)对丝裂霉素 (MMC)体外增效作用。方法 以人宫颈癌Hela细胞和耐药亚系Hela/MMC细胞为材料 ,观察了SDZPSC833和VER对MMC体外增效作用。结果 无毒剂量的SDZPSC833和VER ( 13mg/L)可显著增加MMC的细胞毒作用且可基本克服Hela/MMC细胞对MMC 5 0 2倍的耐药 ;3H -TdR实验表明 ,VER或SDZPSC833与MMC联用可增加MMC对宫颈癌细胞DNA合成的抑制 ,且SDZPSC833作用强于VER ,光镜和电镜下形态学观察 ,联合用药组细胞呈明显退行性变。结论 无毒剂量的SDZPSC833和VER体外能基本逆转Hela/MMC细胞对MMC的耐药性 ,且SDZPSC833作用强于VER。SDZPSC833作为耐药修饰剂可望用于宫颈癌化疗 ,其临床应用前景优于VER。

Objective To determine the reversion of mitomycin(MMC) resistance by SDZ PSC833 and verapamil(VER) in human cervical cancer in vitro.Methods The reversion of mitomycin resistance by SDZ PSC833 or VER was detected for human cervical cancer cell(Hela) and its resistant subline Hela/MMC in vitro.. Results Both nontoxic doses of SDZ PSC833 and VER (1~3mg/L) might enhance the cytotoxicity of MMC in Hela and Hela/MMC and could result in almost complete or partial reversion of MMC-resistance of Hela/MMC. 3H-TdR incorporation test indicated that SDZ PSC833 or VER enhanced the inhibition of DNA synthesis in Hela and Hela/MMC cell.Moreover,the effect of SDZ PSC833 on reversing drug resistance was better than VER in vitro. Conclusions SDZ PSC833 and VER can overcome mitomycin resistance of Hela/MMC in vitro.SDZ PSC833 will be a better candidate for reversing multidrug resistance than verapamil in clinic.