華蟾素聯用順鉑對乳腺癌MDA-MB-231細胞活力、凋亡及周期分布的影響

肖聰 張懿敏 孫圣榮

[摘要] 目的 研究華蟾素聯用順鉑對乳腺癌MDA-MB-231細胞活力、凋亡和細胞周期分布的影響。 方法 體外培養乳腺癌MDA-MB-231細胞。CCK-8法檢測華蟾素聯用順鉑對細胞活力的影響;劃痕實驗檢測華蟾素聯用順鉑對細胞遷移能力的影響;流式細胞術分析華蟾素聯用順鉑對細胞凋亡率及細胞周期分布的影響。 結果 CCK-8結果顯示，與對照組比較，華蟾素組、順鉑組及華蟾素+順鉑組細胞活力降低，差異有統計學意義（P < 0.05或P < 0.01）。劃痕結果顯示，與對照組比較，華蟾素+順鉑組遷移能力顯著下降，差異有高度統計學意義（P < 0.01）。流式結果顯示，與對照組比較，華蟾素+順鉑組G1期比例顯著增多且凋亡更加明顯，差異有統計學意義（P < 0.05或P < 0.01）。 結論 華蟾素聯用順鉑能協同抑制乳腺癌MDA-MB-231細胞活力，可能與誘導細胞周期阻滯于G1期、抑制細胞遷移并促進細胞凋亡有關。

[關鍵詞] 華蟾素;順鉑;乳腺癌;MDA-MB-231細胞

[中圖分類號] R737.9? ? ? ? ? [文獻標識碼] A? ? ? ? ? [文章編號] 1673-7210（2019）07（c）-0012-05

Effect of cinobufacini combined with Cisplatin on cell viability， apoptosis and cell cycle distribution of MDA-MB-231 cells

XIAO Cong*? ?ZHANG Yimin*? ?SUN Shengrong

Department of Breast and Thyroid Surgery， Renmin Hosptial of Wuhan University， Hubei Province， Wuhan? ?430060， China

[Abstract] Objective To study the effects of cinobufacini combined with Cisplatin on cell viability， apoptosis and cell cycle distribution of breast cancer MDA-MB-231 cells. Methods Breast cancer MDA-MB-231 cells were cultured in vitro. CCK-8 assay was used to detect the effect of cinobufacini combined with Cisplatin on cell viability. Scratch test was performed to detect the effect of cinobufacini combined with Cisplatin on cell migration. Flow cytometry was used to analyze the effects of cinobufacini combined with Cisplatin on the apoptosis rate and cell cycle distribution of breast cancer cells. Results CCK-8 results showed that compared with the control group， the cell viability in the cinobufacini group， the Cisplatin group and the cinobufacini+Cisplatin group was decreased， the differences were statistically significant （P < 0.05 or P < 0.01）. The scratch results showed that the migration ability of the cinobufacini+Cisplatin group was significantly decreased compared with the control group， the difference was highly statistically significant （P < 0.01）. Flow cytometry showed that compared with the control group， the proportion of G1 phase in the cinobufacini+Cisplatin group increased significantly and the apoptosis was more obvious， the differences were statistically significant （P < 0.05 or P < 0.01）. Conclusion Cinobufacini combined with Cisplatin shows a synergic effect in inhibiting MDA-MB-231 cells， which may be related to the induction of cell cycle arrest at G1 phase， inhibition of cell migration and promotion of cell apoptosis.

[Key words] Cinobufacini; Cisplatin; Breast cancer; MDA-MB-231 cell

乳腺癌是女性最常見的惡性腫瘤之一，全世界每年發病人數高達167萬例，嚴重威脅女性的身心健康[1-2]。化療作為乳腺癌綜合治療中至關重要的一環，發揮著抑制癌癥進展、延長生存時間等作用[3]。順鉑作為乳腺癌術后化療的一線藥物，近年來許多臨床研究表明，鉑類對于復發的晚期乳腺癌均有較好的客觀緩解率[4-5]。但與其他化療藥類似，順鉑的不良反應表現為骨髓抑制、胃腸道反應、神經毒性、腎臟毒性等，在一定程度上限制了其臨床應用[6]。因此尋求通過藥物聯用降低其使用劑量，從而減少其毒副作用是一種有效的解決手段[7]。華蟾素作為一種中藥，具有活血化瘀、化結潰堅、利水消腫、清熱解毒等功效[8-9]。本課題組前期的研究發現，華蟾素對乳腺癌MDA-MB-231細胞有明顯的抑制作用[10]。徐曉武等[9]研究也發現，華蟾素能誘導乳腺癌MCF-7細胞凋亡，作用機制可能與Bax蛋白表達上調并向線粒體轉位有關。……