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新型四价铂类配合物抑制乳腺癌细胞增殖的机制
新型四价铂类配合物抑制乳腺癌细胞增殖的机制
秦 岩1,2,赵明慧3,霍树营4,石 岩5,魏天铸4,黄胜楠4,刘永莲4,刘小青4,聂子元6,史建红1,2

1 河北大学附属医院中心实验室,保定 071000; 2 河北省放化疗机制与规程研究重点实验室,1 河北大学附属医院中心实验室,保定 071000; 2 河北省放化疗机制与规程研究重点实验室,5 河北大学附属医院肿瘤内科,保定 071000; 6 河北医科大学附属第二医院血液内科,石家庄 050000
Inhibition effects of Pt(IV) on proliferation of breast cancer cells
(1 Department of Central Laboratory, Affiliated Hospital of Hebei University, Baoding 071000, China; 2 The Key Laboratory of Hebei Province, Affiliated Hospital of Hebei University, Baoding 071000, China;2 The Key Laboratory of Hebei Province, Affiliated Hospital of Hebei University, Baoding 071000, China;4 Hebei University, Baoding 071000, China; 5 Department of Medical Oncology, Affiliated Hospitalof Hebei University, Baoding 071000, China; 6 Department of Internal Medicine of Hematology,The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China)

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起始页:69

摘要:[摘要] 目的:研究新型四价铂类配合物Pt(IV)抑制乳腺癌细胞增殖、促凋亡的作用及分子机制。方法:细胞计数法、MTS法、PI单染流式细胞术分别检测细胞活力、增殖、凋亡能力;Western blot检测凋亡相关蛋白、PI3K/Akt和MAPK通路关键蛋白的表达。结果:Pt(IV)能降低乳腺癌细胞MCF-7的活力,抑制MCF-7细胞的增殖。新型四价铂类配合物Pt(IV)也可下调Bcl-2,上调active caspase 3和Bax蛋白表达。进一步研究发现,Pt(IV)同时显著减少p-Akt和p-ERK1/2的蛋白表达。结论:Pt(IV)具有抑制乳腺癌细胞增殖和促进凋亡作用,其作用可能与其调控PI3K/Akt和MAPK通路、抑制Bcl-2和上调active caspase 3和Bax蛋白有关。

关键词:[关键词] 新型四价铂类配合物;乳腺癌细胞;增殖;凋亡;信号通路

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Abstract:[Abstract] Objective: To investigate the effect of Pt(IV) on proliferation and apoptosis of breast cancer cells (MCF-7 cells). Methods: Cell count array, MTS assay and FCM were conducted to assess cell viability, proliferation and apoptosis. Western blotting analysis was used to assay the effect of Pt(IV) on expression of apoptosis-related proteins, and the key proteins in the PI3K/Akt and MAPK pathways. Results: Pt(IV) significantly reduced survival and inhibited proliferation of MCF-7 cells in a dose-dependent manner. Furthermore, Pt(IV) decreased protein expression of Bcl-2 and increased the expression of active caspase 3 and Bax in MCF-7 cells. Pt(IV) down-regulated the levels of p-Akt and p-ERK1/2. Conclusion: Pt(IV) has multiple antitumor effects including inhibition of cell survival and promotion of apoptosis in breast cancer cells. Suppression of p-Akt and p-ERK in the PI3K/Akt and MAPK pathways may be involved in its effect on proliferation and apoptosis of breast cancer cells.

Key words:[Key words] Pt(IV); breast cancer cells; proliferation; apoptosis; signal pathways

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