Effects of As2O3 and Resveratrol on the Proliferation and Apoptosis of Colon Cancer Cells and the hERG-mediated Potential Mechanisms
Effects of As2O3 and Resveratrol on the Proliferation and Apoptosis of Colon Cancer Cells and the hERG-mediated Potential Mechanisms
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As2O3和白藜芦醇对结肠癌细胞增殖和凋亡的影响及hERG介导的潜在机制
DOI：
10.2174/1381612817666190619123610
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发表时间：
2019-01-01
影响因子：
3.1
通讯作者：
Zhao, Xin
中科院分区：
文献类型：
--
作者：
Yan, Caichuan;Li, Fengmei;Zhao, Xin
摘要：背景资料：As2O3和白藜芦醇被广泛认为是有效的抗肿瘤治疗和潜在的机制已被广泛报道。然而，As2O3和白藜芦醇在肿瘤治疗中的联合治疗效果和潜在靶点仍然是未知的。本研究的目的是探讨As2O3联合白藜芦醇治疗结肠癌的益处和疗效，以及寻找新的靶点，可以提供药物疗效的替代解释。研究方法：MTT法和EdU染色法检测癌细胞增殖情况，流式细胞仪检测癌细胞凋亡情况。采用Western blot和免疫沉淀法分别检测hERG和整合素β1蛋白的表达水平及相互作用。结果如下：本研究发现，As2O3和白藜芦醇均能有效抑制结肠癌细胞增殖，促进细胞凋亡，且两种药物联合应用对结肠癌细胞的作用更为突出。As2O3与白藜芦醇联合作用，一方面降低了hERG通道在膜上的表达，另一方面减弱了hERG与整合素β 1的结合，这可能是导致下游信号通路改变，包括激活凋亡通路的主要原因。结论：因此，hERG作为细胞膜钾离子通道的亚基，很可能参与As2O3和白藜芦醇诱导的细胞内信号级联紊乱，这一新的维持结肠癌进展的信号通路可能成为未来结肠癌治疗的一个有希望的靶点。
Abstract: Background: As2O3 and resveratrol have been widely considered to be effective in anti-cancer therapies and the underlying mechanisms have been reported extensively. However, the combined treatment effect and potential target of As2O3 and resveratrol in the treatment of tumors remains elusive. The purpose of this study was to investigate the benefits and efficacy of As2O3 in combination with resveratrol in the treatment of colon cancer, as well as looking for new targets that could provide alternative explanation of the efficacy of drugs. Methods: The proliferation of cancer cells was measured by the MTT and EdU staining assay, while the apoptosis of cancer cells was determined by the flow cytometry. Western blot and immunoprecipitation were performed to measure the expression levels of proteins and the interaction between hERG and integrin β1, respectively. Results: In this study, we found that both As2O3 and resveratrol can effectively inhibit cell proliferation and promote cell apoptosis in colon cancer, and the combined effect of the two drugs on colon cancer cells is more preeminent. The combination of As2O3 with resveratrol, on the one hand reduced the expression of hERG channels on the membrane, and on the other hand weaken the binding between hERG and integrin β 1, which may be the main cause of downstream signaling pathways alterations, including the activation of the apoptotic pathway. Conclusion: Taken together, hERG, as a subunit of potassium ion channel on the cell membrane, is highly likely to be involved in the As2O3 and resveratrol induced intracellular signaling cascade disorder, and this novel signaling pathway that sustains the progression of colon cancer may be a promising therapeutic target for human colon cancer treatment in the future.