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YAP的下调抑制人肝癌细胞的增殖、侵袭并增加顺铂敏感性。

Downregulation of YAP inhibits proliferation, invasion and increases cisplatin sensitivity in human hepatocellular carcinoma cells.

作者信息

Wang Xiaoguang, Wu Bin, Zhong Zhengxiang

机构信息

Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Jiaxing Medical College, Jiaxing, Zhejiang 314000, P.R. China.

出版信息

Oncol Lett. 2018 Jul;16(1):585-593. doi: 10.3892/ol.2018.8633. Epub 2018 May 4.

Abstract

Yes-associated protein (YAP) serves an essential role in tumorigenesis. However, the potential role and the molecular mechanism underlying the effect of YAP on hepatocellular carcinoma (HCC) cells have not been elucidated. In the current study, it was revealed that YAP expression was increased significantly in HCC cancer tissues and its overexpression was associated with tumor differentiation. The silencing of YAP by small interferring RNA led to the inhibition of HCC cell growth, which was associated with the promotion of apoptosis. The silencing of YAP also decreased the invasive potential of HCC cells and the activity of the phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) signaling pathway. Furthermore, silencing of YAP increased the chemosensitivity of HCC cells to cisplatin (CDDP) through inactivation of the PI3K/AKT signaling pathway. studies using PDTX model suggested a promotive role for YAP in the growth of HCC and knockdown of YAP increased the anti-tumor activity of CDDP. Taken together, these results revealed that YAP is overexpressed in HCC, and promotes proliferation, invasion and drug resistance of HCC cells. Inhibition of YAP, alone or in combination with traditional chemotherapy, may effectively combat HCC.

摘要

Yes相关蛋白(YAP)在肿瘤发生过程中发挥着重要作用。然而,YAP对肝癌(HCC)细胞作用的潜在作用及分子机制尚未阐明。在本研究中,发现YAP在肝癌组织中表达显著增加,其过表达与肿瘤分化相关。小干扰RNA沉默YAP导致肝癌细胞生长受到抑制,这与细胞凋亡的促进有关。YAP的沉默还降低了肝癌细胞的侵袭能力以及磷酸肌醇3激酶(PI3K)/AKT丝氨酸/苏氨酸激酶(AKT)信号通路的活性。此外,YAP的沉默通过使PI3K/AKT信号通路失活增加了肝癌细胞对顺铂(CDDP)的化疗敏感性。使用人源肿瘤异种移植(PDTX)模型的研究表明YAP在肝癌生长中起促进作用,敲低YAP可增强CDDP的抗肿瘤活性。综上所述,这些结果表明YAP在肝癌中过表达,并促进肝癌细胞的增殖、侵袭和耐药性。抑制YAP,单独或与传统化疗联合使用,可能有效对抗肝癌。

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