人卵巢癌细胞阿霉素耐药株的建立及其耐药机制的探讨

ESTABLISHMENT OF ADRIAMYCIN-RESISTANT HUMAN OVARIANCARCINOMA CELL LINE AND ITS MECHANISM OF MULTIDRUG RESISTANCE

人卵巢癌阿霉素耐药细胞株是用Ａ２７８０人卵巢癌细胞株作亲本，获得的能耐受０．８μｇ．ｍｌ－１ＡＤＭ的细胞株Ａ２７８０／ＡＤＭ。此细胞株对ＡＤＭ的耐受程度约为Ａ２７８０细胞的１７倍。对其他抗肿瘤药如长春新碱、鬼臼乙叉甙有明显的交叉耐药，对５－氟脲嘧啶、顺铂、米尔法兰则无明显交叉耐药性。进一步研究表明耐药株对ＡＤＭ蓄积明显减少；免疫细胞化学的研究显示：Ａ２７８０／ＡＤＭ细胞中Ｐ－１７０膜蛋白和谷胱甘肽Ｓ－转移酶（ＧｓＴ－π）均较Ａ２７８０表达高。对耐药的逆转也进行了初步研究，发现维拉帕米与ＡＤＭ合用能提高Ａ２７８０／ＡＤＭ细胞对ＡＤＭ的药物敏感性，细胞的耐受性得到部分逆转。

Amultidrug-resistant cell line(A278/ADM)of human ovarian carcinoma which can resist 0.8μg· ml-1 of adriamycin(ADM)was obtained by step-wise selection exposure toincreasing doses of ADM,A2780/ADM cells showed 17-fold higher resistance to ADM than A2780 cells。The doubling times were43.8 h in A2780/ADM and 26.3 h in A2780 cells.Colony formationrates were l5%～ 20%in A2780/ADM and 65%～75%in A2780 cells. A2780/ADM cell line wasalso shown to significantly cross-resistant to vincristine(VCR) and VP-1 6,but no cross-resistancewas found to 5一Fu,PDD or Mel。A further investigation showed that intracellular accumulation of ADM in A2780/ADM wassignificantly decreased.Expressions of Pglycoprotein and GST-π:were increased in A2780/ADM bymeans of immunohistochemical method。Verapamil(Ver)combined with ADM was found to increasethe sensitivity and reverse the resistance to ADM in A2780/ADM,This study indicates that A2780ADM has the peculiarity of multidrug resistance and there may be other mechanism of drug-resistancebesides MDR related to P-1 70。