目的 评价白首乌新苷A(CA)的体内外抗肿瘤活性及诱导肿瘤细胞凋亡的作用。方法 以3种人肿瘤细胞株为模型,用MTT 法检测药物对肿瘤细胞增殖的影响;以小鼠移植性肉瘤S₁₈₀ 为模型,检测药物对在体肿瘤生长的影响;以人乳腺癌细胞株MCF-7为模型,用Wright′s-Giemsa 染色观察药物对细胞核形态的影响,并用流式细胞仪检测肿瘤细胞凋亡率;以体外培养的大鼠皮层神经元细胞为模型,评价药物对正常细胞的毒性。结果 CA 对3种人肿瘤细胞株的生长呈浓度依赖性抑制,其半数抑制浓度(IC₅₀)为35.68-39.78mg/L;CA 40、80、160mg/kg 对S180内瘤生长的抑制率分别为20.0%、28.0%、48.1%;CA 80mg/L 处理后,MCF-7细胞的凋亡率显著增高(P<0.01),细胞核出现固缩、断裂;CA 100mg/L 对体外培养8d的神经元无毒性。结论 CA 有明显的体内外抗肿瘤活性,诱导肿瘤细胞凋亡是其作用机制之一。

Objective To investigate the antitumor effect of cynanauriculoside A(CA) isolated from the root of Cynanchum auriculatum and its effect of apoptosis induction in tumor cells.Methods CA was evaluated for its cytotoxicity in vitro against MCF-7,BEL-7402,and HO-8910 cells by determining MTT assay and its antitumor effects in vivo on S180 tumor-bearing mice by calculating tumor-inhibited rate.Measures of apoptosis including Wright′s-Giemsa staining and flow cytometry(FCM) assay were involved to explore the mechanism.And the toxcity of CA on normal cells was also evaluated on in vitro cultured rat cortical neurons.Results CA showed a definite cytotoxicity to three tumor cell lines with IC₅₀ in the range of 35.68-39.78mg/L.And it significantly inhibited the tumor growth of S₁₈₀ tumor-bearing mice at the dose of 40,50,and 160mg/kg by ig administrated,the inhibitory rates were 20.0%,28.0%,and 48.1%,respectively.At the concentration of 80mg/L,CA induced obvious apoptosis in MCF-7 cells(P<0.01) associated with marked morphological changes such as cytoplasm contraction and nuclear chromatin condensation,while it showed no toxcity to rat cortical neurons cultured 8d in vitro at the concentration of 100 mg/L.Conclusion CA has significant antitumor effect in vitro[WTBZ] and in vivo,and has moderate effect of inducing tumor cells apoptosis,which may be one of the mechanisms of CA antitumor activity.

浙江省自然科学基金重点项目资助(ZD0016)