miR-200c enhances sensitivity of drug-resistant non-small cell lung cancer to gefitinib by suppression of PI3K/Akt signaling pathway and inhibites cell migration via targeting ZEB1

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• 作者：Guohua Zhou^a ; Fangli Zhang^a ; Yu Guo^a ; Jianfei Huang^a ; Yaqiong Xie^a ; Shuanglei Yue^a ; Minghui Chen^a ; Hao Jiang^b ; Mengjie Li^c ; ^{522237197@qq.com}
• 关键词：miR-200c ; Drug-resistance ; NSCLC ; PI3K
• 刊名：Biomedicine & Pharmacotherapy
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：85
• 期：Complete
• 页码：113-119
• 全文大小：1615 K
• 卷排序：85

文摘

Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is a major obstacle in the treatment of non-small cell lung cancer (NSCLC) patients. We explored the role of miR-200c in modulating the sensitivity of gefitinib-resistant NSCLC cells and examined the underlying mechanism. The gefitinib-resistant cell line PC-9-ZD and its parental PC-9 cells were used. Growth inhibition was detected by MTT assay. The cell apoptosis was detected by Annexin V/PI assay. Cell migration was assessed by wound-healing assay. RT-PCR was used to detected levels of miR-200c and ZEB1. The PI3k, Bcl-2, Bax, caspase-3 and ZEB1 protein expression were detected using Western blot analysis, and TUNEL, Immunohistochemistry for xenograft model. PC-9-ZD cells had low level of miR-200c expression compared to its parental PC-9 cells. PC-9-ZD cells with miR-200c transfection were more sensitive to gefitinib treatment. Apoptosis induced by gefitinib was observed in PC-9-ZD cells with miR-200c transfection significantly. The levels of phosphorylated-Akt and Bcl-2 expression decreased and levels of Bax and Caspase-3 expression increased in PC-9-ZD cells with miR-200c transfection. Cell migration was inhibited and ZEB1 mRNA level and protein expression were significantly decreased in PC-9-ZD cells with miR-200c transfection. Further in gefitinib resistant xenograft model, miR-200c enhanced sensitivity of gefitinib and induced apoptosis significantly through PI3K/Akt signaling pathway and targeting ZEB1. These results provided insights into the functions of miR-200c and offered an alternate approach in treating gefitinib-resistance NSCLC.