新型雌激素化合物17aα-D-高炔雌二醇-3-乙酯抗肿瘤活性的初步研究

Initial Study on Anti-tumor Activities of Novel Estrogen Compound 17aα-D-Homo-Ethynylestradiol-3-Acetate

目的对新型雌激素化合物17aα-D-高炔雌二醇-3-乙酯进行体外和体内的抗肿瘤活性实验研究。方法采用MTT法进行药物体外对肺腺癌细胞A549和人肝癌细胞Bel-7402抗肿瘤实验,测定IC50;体内对小鼠肺腺癌LA795抑制作用采用常规抗肿瘤实验方法进行,腹腔给药观察抑瘤率,胸腺及脾重量、指数的变化。结果17aα-D-高炔雌二醇-3-乙酯体外肺腺癌细胞A549和人肝癌细胞Bel-7402的IC50分别为12.28μg·mL-1、17.79μg·mL-1;体内对小鼠肺腺癌LA795实体瘤最佳抑制率达60.0%,各给药组与空白对照组比较有非常显著性差异(P<0.01);脏器重量及指数与空白对照组比较无显著差异,而与阳性对照药环磷酰胺(CY)组存在显著性差异(P<0.01)。结论17aα-D-高炔雌二醇-3-乙酯体外和体内对实验肿瘤均有明显的抗肿瘤活性,而且在给药剂量下对实验动物未表现出任何毒性反应,值得深入研究。

OBJECTIVE The paper reports experimental research on anti-tumor activities of the novel estrogen compound 17aα-D-homo ethynylestradiol-3-acetate in vitro and in vivo. METHODS In vitro antitumor assay were performed to pulmonary adenoma cells A549 and human liver cancer cells Bel-7402, MTT method was employed and half-inhibitory concentrations （IC50were observed. In vivo assay the pulmonary adenoma LA795 was selected and the conventional assay method was employed. 17aα-D-homo ethynylestradiol- 3 acetate was administered by iv. way, and tumor-inhibitory rate, weights and indexes of thymus gland and Spleen were observed. RESULTS IC50 of 17aα-D-homo-ethynylestradiol-3-acetate in vitro to A549 and Bel-7402 cells were 12.28μg · mL^-1 and 17.79μg · mL^-1 ,respectively. In vivo the best tumor-inhibitory rates to LA795 was 60. 0%, with very obvious difference （P 〈0. 01） compared with control mice. The drug has hard/y any influence to spleen and thymus gland weights ,indexes compared with control mice. Nevertheless, compared with the positive control drug CY, thymus gland and spleen weights, indexes have obvious difference （P〈0.01） . CONCLUSION 17aα-D-homo ethynylestradiol-3-acetate has obvious anti-tumor activities in vitro and in vivo, and has not shown any toxic response to experiment mice under the administered dosage, worth further investigation.