溫陽散結中藥干預乳腺癌細胞SK—BR—3的生長抑制及誘導凋亡研究

劉曉菲+李靜蔚+時光喜

[摘要] 目的 研究體外實驗中陽和化巖湯與曲妥珠單抗及PI3K抑制劑LY294002對乳腺癌細胞株SK-BR-3（HER-2高表達型）的增殖抑制及誘導凋亡作用。 方法 制備溫陽散結方腸吸收液，將SK-BR-3乳腺癌細胞株分為空白對照組、中藥組、曲妥珠組、曲妥珠+中藥組、Ly組、Ly+中藥組。MTT法觀察24、48、72 h藥物對細胞的生長抑制率，流式細胞儀測定藥物干預72 h后細胞凋亡率和細胞周期的變化。 結果 與空白對照組相比，中藥組、曲妥珠組、曲妥珠+中藥組、Ly組、Ly+中藥組細胞抑制率和細胞凋亡率增加，S期細胞比例明顯增高，G2/M期呈下降趨勢（P < 0.05）。且各給藥組細胞抑制率隨著藥物作用時間延長（24、48、72 h）逐漸增加，呈現時間依賴效應（P < 0.05）。曲妥珠+中藥組、Ly+中藥組抑制細胞增殖、誘導細胞凋亡及阻滯細胞周期的作用分別優(yōu)于單純曲妥珠組、Ly組（P < 0.05）。 結論 陽和化巖方腸吸收液能夠有效抑制細胞增殖及誘導凋亡，聯(lián)合曲妥珠及LY能夠進一步抑制細胞增殖的能力、誘導細胞凋亡能力、增強S期阻滯，抑制細胞進入G2/M期，提示溫陽散結中藥聯(lián)合曲妥珠及PI3K抑制劑治療HER-2高表達型乳腺癌可能存在協(xié)同作用。

[關鍵詞] 溫陽散結法；陽和化巖湯；HER-2高表達型乳腺癌；生長抑制；細胞凋亡；曲妥珠單抗；PI3K抑制

[中圖分類號] R285.5 [文獻標識碼] A [文章編號] 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