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沉默 PINK1 抑制肺癌细胞的生长、迁移并诱导其凋亡。

Silencing of PINK1 represses cell growth, migration and induces apoptosis of lung cancer cells.

机构信息

Department of Respiratory Medicine, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121001, People's Republic of China.

Department of Anatomy, Histology and Embryology, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People's Republic of China.

出版信息

Biomed Pharmacother. 2018 Oct;106:333-341. doi: 10.1016/j.biopha.2018.06.128. Epub 2018 Jul 11.

Abstract

PTEN induced putative kinase 1 (PINK1) has been found to be up-regulated, which promotes the proliferation and chemoresistance in lung cancer. Nevertheless, the role and detailed mechnisms of PINK1 in lung cancer have not been fully understood, which need to be further clarified. In this study, the resluts showed that silencing of PINK1 inhibited proliferation and blocked cell cycle of lung cancer cells. Furthermore, the apoptosis rate was enhanced by PINK1 suppression, as evidenced by increased protein levels of Bax, cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP), and decreased level of Bcl-2. The migration and invasion abilities were also restrained by PINK1 silencing. Silencing of PINK1 also resulted in oxygen species (ROS) overproduction and decreased mitochondrial membrane potential. Finally, suppression of PINK1 repressed the growth of xenograft tumor and induced apoptosis in tumor tissues in vivo. This study might lead to PINK1 kinase as a novel therapeutic target for lung cancer treatment.

摘要

PTEN 诱导假定激酶 1(PINK1)被发现上调,这促进了肺癌的增殖和化疗耐药性。然而,PINK1 在肺癌中的作用和详细机制尚未完全阐明,需要进一步阐明。在这项研究中,结果表明沉默 PINK1 抑制了肺癌细胞的增殖并阻断了细胞周期。此外,通过抑制 PINK1,细胞凋亡率增加,这表现为 Bax、cleaved caspase-3 和 cleaved 多聚(ADP-核糖)聚合酶(PARP)的蛋白水平增加,Bcl-2 水平降低。迁移和侵袭能力也受到 PINK1 沉默的抑制。沉默 PINK1 还导致氧物种(ROS)产生过多和线粒体膜电位降低。最后,抑制 PINK1 抑制了异种移植肿瘤的生长并诱导了体内肿瘤组织的凋亡。这项研究可能导致 PINK1 激酶成为治疗肺癌的新的治疗靶标。

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