温阳散结中药干预乳腺癌细胞SK—BR—3的生长抑制及诱导凋亡研究

刘晓菲+李静蔚+时光喜

[摘要] 目的 研究體外实验中阳和化岩汤与曲妥珠单抗及PI3K抑制剂LY294002对乳腺癌细胞株SK-BR-3（HER-2高表达型）的增殖抑制及诱导凋亡作用。 方法 制备温阳散结方肠吸收液，将SK-BR-3乳腺癌细胞株分为空白对照组、中药组、曲妥珠组、曲妥珠+中药组、Ly组、Ly+中药组。MTT法观察24、48、72 h药物对细胞的生长抑制率，流式细胞仪测定药物干预72 h后细胞凋亡率和细胞周期的变化。 结果 与空白对照组相比，中药组、曲妥珠组、曲妥珠+中药组、Ly组、Ly+中药组细胞抑制率和细胞凋亡率增加，S期细胞比例明显增高，G2/M期呈下降趋势（P < 0.05）。且各给药组细胞抑制率随着药物作用时间延长（24、48、72 h）逐渐增加，呈现时间依赖效应（P < 0.05）。曲妥珠+中药组、Ly+中药组抑制细胞增殖、诱导细胞凋亡及阻滞细胞周期的作用分别优于单纯曲妥珠组、Ly组（P < 0.05）。 结论 阳和化岩方肠吸收液能够有效抑制细胞增殖及诱导凋亡，联合曲妥珠及LY能够进一步抑制细胞增殖的能力、诱导细胞凋亡能力、增强S期阻滞，抑制细胞进入G2/M期，提示温阳散结中药联合曲妥珠及PI3K抑制剂治疗HER-2高表达型乳腺癌可能存在协同作用。

[关键词] 温阳散结法；阳和化岩汤；HER-2高表达型乳腺癌；生长抑制；细胞凋亡；曲妥珠单抗；PI3K抑制

[中图分类号] R285.5 [文献标识码] A [文章编号] 1673-7210（2018）01（b）-0013-04

[Abstract] Objective To research the inhibit proliferation and induce apoptosis effect of Yanghe Huayan Decoction combined with Trastuzumab and PI3K inhibitor （LY294002） on breast cancer cell lines SK-BR-3 （HER-2 overexpression）. Methods The intestinal absorption fluid of Yanghe Huayan Decoction was prepared. The breast cancer cell lines SK-BR-3 were divided into blank control group， Chinese medicines group， Trastuzumab group， Trastuzumab + Chinese medicines group， Ly group and Ly + Chinese medicine group. The inhibitory rate of the growth of the cells at 24， 48， 72 h were observed by MTT. The changes of cell apoptosis and cell cycle at 72 h were observed by flow cytometry. Results The inhibition rate， apoptosis rate and S phase cell percentage were increased， while the G2/M phase cell percentage was decreased， in the Chinese medicine group， Trastuzumab group， Trastuzumab + Chinese medicine group， Ly group and the Ly + Chinese medicine group， compared with the blank control group， with statistically significant difference （P < 0.05）. Moreover， the inhibition rate of each drug group was increased gradually with the duration of drug action （24， 48， 72 h）， presenting a time dependent effect （P < 0.05）. The effects of the Trastuzumab group + Chinese medicine， Ly + Chinese medicine group inhibiting cell proliferation， inducing apoptosis and cell cycle arrest were better than those of the Trastuzumab group， Ly group respectively （P < 0.05）. Conclusion The intestinal absorption fluid of Yanghe Huayan Decoction can effectively inhibit cell proliferation and induce apoptosis， and the combination of Chinese medicine with Trastuzumab and LY can further inhibit cell proliferation， induce apoptosis， enhance S phase retardation， and inhibit cell entry into G2/M phase. It is suggested that there may be synergistic effect in the treatment of her-2 high expression type of breast cancer by the combination of warming Yang and dispersing masses herbs with Trastuzumab and PI3K inhibitor.endprint