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沉默Rab27a基因对非小细胞肺癌生物学特性及化疗敏感性的影响

Effects of silencing Rab27a gene on biological characteristics and chemosensitivity of non-small cell lung cancer.

作者信息

Li Xia, Wang Haiying, Ni Qinggan, Tang Zhiyuan, Ni Jun, Xu Liqin, Huang Hua, Ni Songshi, Feng Jian

机构信息

Department of Respiratory, Yancheng Third People's Hospital, Yancheng 224002, Jiangsu, China.

Department of Respiratory, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.

出版信息

Oncotarget. 2017 Oct 10;8(55):94481-94492. doi: 10.18632/oncotarget.21782. eCollection 2017 Nov 7.

Abstract

Rab27a, a member of the Rab protein family, can regulate the tumor microenvironment and promote the development of the tumor. Elevated expression of Rab27a is closely connected with many human cancers containing non-small cell lung cancer (NSCLC). But the role of Rab27a in non-small cell lung cancer and its possible mechanism is particularly unclear. In this research, we explored the effect of silencing Rab27a and , furnishing evidence that Rab27a could be a potential therapeutic target in NSCLC. Compared with corresponding control cells, silencing Rab27a had decreased ability of cell proliferation, migration and invasion and slower growth of xenograft tumors in mice. The expressions of apoptosis-associated proteins were induced with a reduction of anti-apoptotic protein in the NSCLC cells down-regulated Rab27a. Furthermore, Rab27a was associated with resistance to conventional chemotherapeutic agents. Our findings suggested that Rab27a might play a critical role in increasing chemosensitivity in NSCLC.

摘要

Rab27a是Rab蛋白家族的成员之一,可调节肿瘤微环境并促进肿瘤发展。Rab27a表达升高与包括非小细胞肺癌(NSCLC)在内的多种人类癌症密切相关。但Rab27a在非小细胞肺癌中的作用及其可能机制尚不清楚。在本研究中,我们探究了沉默Rab27a的效果,提供了Rab27a可能成为NSCLC潜在治疗靶点的证据。与相应的对照细胞相比,沉默Rab27a降低了细胞增殖、迁移和侵袭能力,并且小鼠体内异种移植瘤的生长也减缓。在下调Rab27a的NSCLC细胞中,凋亡相关蛋白的表达被诱导,同时抗凋亡蛋白减少。此外,Rab27a与对传统化疗药物的耐药性有关。我们的研究结果表明,Rab27a可能在提高NSCLC化疗敏感性方面起关键作用。

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