Knockdown of insulin-like growth factor I receptor inhibits the growth and enhances chemo-sensitivity of liver cancer cells.
Knockdown of insulin-like growth factor I receptor inhibits the growth and enhances chemo-sensitivity of liver cancer cells.
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DOI：
10.2174/156800912798888974
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发表时间：
2012
影响因子：
3
通讯作者：
Ye-wei Zhang;D. Yan;Wei Wang;H-W Zhao;Xin Lu;J. Wu;Jin-Rong Zhou
中科院分区：
文献类型：
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作者：
Ye-wei Zhang;D. Yan;Wei Wang;H-W Zhao;Xin Lu;J. Wu;Jin-Rong Zhou
肝癌是世界范围内最常见的恶性肿瘤之一。全身化疗仍然是主要的治疗选择，但有严重的不良反应。全身治疗与靶向治疗的组合可以提供有效的治疗。本研究的目的是证明胰岛素样生长因子-I受体（IGF-IR）是否可以作为肝癌治疗的功能靶点，并研究IGF-IR下调的化学增敏活性。IGF-IR敲低通过用IGF-IR小干扰RNA（siRNA）稳定转染肝癌细胞来实现。IGF-IR基因敲低导致肝癌细胞生长、克隆存活、粘附和迁移减少，并增加肝癌细胞对肿瘤诱导剂和化疗药物的体外敏感性。在动物研究中，IGF-IR敲低和阿霉素（ADM）治疗都显着降低了肝肿瘤的生长。IGF-IR基因敲低可通过进一步抑制肿瘤血管生成和诱导肿瘤细胞凋亡增强ADM对肿瘤生长的作用。IGFIR-siRNA组、ADM处理的EGFP组和ADM处理的IGFIR-siRNA组的最终肿瘤尺寸与EGFP对照组相比分别显著减小52.5%、33.8%和86.3%，表明ADM和IGF-IR敲低以协同方式抑制肝肿瘤的生长。这些结果支持IGF-IR可以作为肝癌治疗的功能性分子靶点，并且全身化疗与靶向IGF-IR抑制的组合可以提供肝癌的有效治疗策略。
Liver cancer is one of the most common malignant cancers worldwide. Systemic chemotherapy remains the major treatment option, but with severe adverse effects. Combinations of systemic with targeted treatments may provide effective therapeutics. The objectives of this study were to demonstrate if insulin-like growth factor-I receptor (IGF-IR) might serve as a functional target for liver cancer treatment and to investigate the chemo-sensitizing activity of IGF-IR downregulation. IGF-IR knockdown was achieved by stable transfection of liver cancer cells with IGF-IR small interfering RNA (siRNA). IGF-IR knockdown resulted in reduced growth, clonogenic survival, adhesion and migration of liver cancer cells, and increased sensitivities of liver cancer cells to apoptosis-inducing agents and chemotherapeutic drugs in vitro. In the animal studies, both IGF-IR knockdown and adriamycin (ADM) treatment significantly reduced the growth of liver tumors. IGF-IR knockdown enhanced the effect of ADM on tumor growth by further reducing tumor angiogenesis and inducing tumor cell apoptosis. The final tumor sizes in the IGFIR-siRNA, ADM-treated EGFP, and ADM-treated IGFIR-siRNA groups were significantly reduced by 52.5%, 33.8%, and 86.3%, respectively, compared with that in the EGFP control, suggesting that the ADM and the IGF-IR knockdown inhibit the growth of liver tumors in a synergistic manner. These results support that IGF-IR may serve as a functional molecular target for liver cancer treatment, and that the combination of systemic chemotherapy with targeted IGF-IR suppression may provide an effective treatment strategy for liver cancer.