Combinational treatment with microRNA‑133b and cetuximab has increased inhibitory effects on the growth and invasion of colorectal cancer cells by regulating EGFR.
Combinational treatment with microRNA‑133b and cetuximab has increased inhibitory effects on the growth and invasion of colorectal cancer cells by regulating EGFR.
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DOI：
10.3892/mmr.2015.4046
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发表时间：
2015-10
影响因子：
3.4
通讯作者：
Jianyu Zhou;L. Lv;Changwei Lin;G. Hu;Yihang Guo;Meirong Wu;Buning Tian;Xiaorong Li
中科院分区：
文献类型：
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作者：
Jianyu Zhou;L. Lv;Changwei Lin;G. Hu;Yihang Guo;Meirong Wu;Buning Tian;Xiaorong Li
结直肠癌（CRC）是第三大最常见的癌症，其预后非常差，主要是由于其高肿瘤侵袭和迁移率，以及对抗表皮生长因子受体（EGFR）治疗的抗性。虽然CRC已被广泛研究，但其潜在的分子机制仍有待阐明。MicroRNA（miR）-133 b已被证明通过调节EGFR在几种人类癌症类型中起肿瘤抑制剂的作用。然而，miR-133 b和EGFR在CRC细胞中的详细参与仍有待阐明。本研究使用逆转录定量聚合酶链反应，并表征了CRC组织和细胞系中miR-133 b表达水平的下调。细胞功能分析表明，miR-133 b的恢复表达抑制了CRC细胞的生长和侵袭。此外，荧光素酶报告基因分析显示，miR-133 b直接靶向EGFR并抑制其在CRC细胞中的表达水平。此外，与miR-133 b模拟物和单克隆抗EGFR抗体西妥昔单抗联合治疗（西妥昔单抗已被批准并经常用于治疗CRC患者），与单独治疗相比，对CRC细胞生长和侵袭的抑制作用有所改善。综上所述，本研究描述了miR-133 b/EGFR相互作用在CRC细胞中的作用，这表明西妥昔单抗和miR-133 b的联合治疗是积极的，可能是未来CRC患者的潜在新治疗方法。
Colorectal cancer (CRC) is the third most common cancer with a very poor prognosis predominantly due to its high rate of tumor invasion and migration, and its resistance to anti‑epidermal growth factor receptor (EGFR) therapy. Although CRC has been widely studied, the underlying molecular mechanism remains to be elucidated. MicroRNA (miR)‑133b has been demonstrated to act as a tumor suppressor in several human cancer types by regulating EGFR. However, the detailed involvement of miR‑133b and EGFR in CRC cells remain to be elucidated. The present study used reverse transcription quantitative polymerase chain reaction and characterized the downregulation of the expression levels of miR‑133b in CRC tissues and cell lines. Cell functional assays demonstrated that restored expression of miR‑133b inhibited the growth and invasion of CRC cells. In addition, a luciferase reporter assay revealed that miR‑133b directly targeted EGFR and repressed its expression levels in CRC cells. Additionally, combination treatment with miR‑133b mimics and the monoclonal anti‑EGFR antibody, cetuximab, which is approved and frequently used for treating patients with CRC, exhibited improved inhibitory effects on the growth and invasion of CRC cells compared with treatment with either alone. Taken together, the present study characterized the role of the miR‑133b/EGFR interaction in CRC cells and this suggested the combinational therapy with cetuximab and miR‑133b was positive and may be a potential novel treatment for patients with CRC in the future.