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首页> 外文期刊>Journal of Cellular Physiology >Gefitinib resistance in HCC mahlavu cells: Upregulation of CD133 expression, activation of IGF-1R signaling pathway, and enhancement of IGF-1R nuclear translocation
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Gefitinib resistance in HCC mahlavu cells: Upregulation of CD133 expression, activation of IGF-1R signaling pathway, and enhancement of IGF-1R nuclear translocation

机译：吉非替尼耐药肝癌mahlavu细胞:Upregulation CD133的表达,激活IGF-1R信号通路和增强IGF-1R核易位

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摘要

Hepatocellular carcinoma (HCC) is the major form of primary liver cancer which accounts for more than half million deaths annually worldwide. While the incidence of HCC is still on the rise, options of treatment are limited and the overall survival rate is poor. The acquisition of cancer drug resistance remains one of the key hurdles to successful treatment. Clearly, a thorough understanding of the underlying mechanisms is needed for new strategies to design novel treatments and/or to improve the current therapies. In the present study, we examined the expression of cancer stem cell (CSC) marker CD133, the activation of insulin-like growth factor 1 receptor (IGF-1R) signaling, and the nuclear translocation of IGF-1R in HCC Mahlavu cells under the treatment of gefitinib, a cancer drug that inhibits epidermal growth factor receptor (EGFR) pathway. Our results demonstrated that Mahlavu cells exhibited strong gefitinib resistance and the CD133 expression level was dramatically increased (from 3.88% to 32%) after drug treatment. In addition, the gefitinib treated cells displayed increased levels of phosphorylation in IGF-1R and Akt, indicating the intensified activation of this cancer-associated signaling pathway. Moreover, we revealed that IGF-1R underwent nuclear translocation in gefitinib treated cells using confocal microscopy. The IGF-1R nuclear translocation was enhanced under gefitinib treatment and appeared in a dose-dependent manner. Our findings suggest that increased IGF-1R nuclear translocation after gefitinib treatment may contribute to the drug resistance and IGF1-R activation, which might also associate with the upregulation of CD133 expression.
机译：肝细胞癌(HCC)是主要的形式原发性肝癌占更多超过一半的全球每年数百万人死亡。在肝细胞癌的发病率仍在上升,选择是有限的和整体的治疗存活率很差。耐药性的关键障碍之一成功的治疗。理解底层机制需要新的策略来设计新颖治疗和/或改善当前疗法。癌症干细胞的表达(CSC)标记CD133,激活胰岛素样生长因子1受体(IGF-1R)信号,在HCC Mahlavu IGF-1R核易位癌症细胞的治疗下,吉非替尼药物抑制表皮生长因子受体(EGFR)的途径。Mahlavu细胞表现出强烈的吉非替尼阻力和CD133的表达水平显著增加(从3.88%到32%)药物治疗。治疗细胞显示水平的提高磷酸化IGF-1R和Akt的指示强化激活癌症相关信号通路。IGF-1R经历了核易位吉非替尼治疗细胞使用共焦显微镜。增强在吉非替尼治疗,出现了剂量依赖性的方式。增加IGF-1R核易位吉非替尼治疗可能导致药物阻力和IGF1-R激活,这可能还与upregulation CD133表达式。

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