科研之友
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摘要
Currently, arsenic has been clinically investigated as a therapeutic agent for a variety of solid malignancies, including breast cancer. However, the exact underlying molecular mechanisms through which arsenic trioxide (As2O3) induces cell growth arrest and apoptosis in solid tumors have not been clearly understood. The aim of our study was to gain an insight into the effect of As2O3 on the human breast cancer MCF-7 cell line and investigate cell growth inhibition, apoptosis, and the molecular mechanism after As2O3 treatment in MCF-7 cells. Expression of FOXO3a, nuclear-FOXO3a, caspase-3, and I kappa B kinase beta (IKK beta) mRNA levels in MCF-7 cells was determined by reverse transcription-polymerase chain reaction (RT-PCR). The protein expression was examined by the Western blot analysis and immunocytochemical staining. The distribution of apoptotic cells was assessed by flow cytometry, and the morphology of the apoptotic cells was investigated by Hoechest33258 staining. Our results showed that As2O3 significantly induced the apoptosis of MCF-7 cells tested in this study in a dose-dependent manner. As2O3 induced the decrease of IKK beta expression and the increase of total as well as nuclear FOXO3a expression, which triggered the phosphorylation of cytoplasmic FOXO3a at the Thr32 residue decrease. RT-PCR, Western blot analysis, and immunocytochemistry revealed that the expression of IKK beta in MCF-7 cells was upregulated when As2O3 was combined with tumor necrosis factor-alpha (TNF-alpha), whereas the expression of FOXO3a was downregulated in comparison with the As2O3-alone group. These findings indicated a specific molecular mechanism by which MCF-7 cell lines were susceptible to the As2O3 therapy through FOXO3a expression and localization. This FOXO3a accumulation may be well correlated with the As2O3-induced reduction of active IKK beta, which may provide new insights into As2O3-related signaling activities.
- 出版日期2012-10
- 单位中国疾病预防控制中心; 徐州医科大学
