阿霉素在小鼠体内诱导S－180细胞株抗药性的实验研究

Development of adriamycin-resistant S-180 cells in mice

利用ＢＡＢＬ／ｃ小鼠，腹腔接种Ｓ－１８０瘤细胞，阿霉素腹腔注射治疗１５个周期培育传代，得到抗阿霉素的Ｓ－１８０细胞株（Ｓ－１８０Ｒ）。此抗药细胞对阿霉素的抗药性比亲本细胞提高６６倍。对典型的ＤＮＡ拓扑异构酶Ⅱ抑制刻ＶＰ１６（Ｅｔｏｐｏｓｉｄｅ）抗药性增加９倍。经免疫组化进一步证实，抗药细胞显示多药抗药基因（ＭＤＲｇｅｎｅ）产物Ｐ－１７０糖蛋白过表达。流式萤光细胞仪测试结果也表明抗药细胞比亲本细胞排出药物能力提高８９倍。可以肯定这是ＭＤＲ基因过表达产物所致。本工作为筛选有效逆转抗药功能的药物及其他治疗手段提供了有用的动物模型。

BALB/c mice inoculated with S-180 cells were chemotherapied with adriamycin in low dosage,for 15 cycles,and resistant cells (S-180R) were obtained.The resistance of these cells against adriamycin was 66 times greater than that of their parent cells.The resistance to a typical DNA topoisomerase II inhibitor VP16(Etoposide) was increased 9 times.Overexpression of multidrug resistant gene(MDR genes) products,P-glycoproteins(P-170),was demostrated by immunohistochemistry,Furthermore,the ability of the resistant cells to reduce net cellular drug accumulation,which was measured with flow fluorescence cytometry,was 89 times higher than that of their parent cells.All these confirmed that the resistance to adriamycin of S-108R cells mainly due to the overexpression of P-glycoproteins.These newly developed S-180 cells will be useful in selection of drugs or some other therapeutic strategies to reverse multidrug resestance in vivo.