Oncotarget

Research Papers:

Clinical implication of voltage-dependent anion channel 1 in uterine cervical cancer and its action on cervical cancer cells

Chih-Hsien Wu, Yu-Wen Lin, Tzu-Fan Wu, Jiunn-Liang Ko and Po-Hui Wang _

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Oncotarget. 2016; 7:4210-4225. https://doi.org/10.18632/oncotarget.6704

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Abstract

Chih-Hsien Wu1, Yu-Wen Lin1, Tzu-Fan Wu1, Jiunn-Liang Ko1, Po-Hui Wang1,2,3

1Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan

2Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan

3School of Medicine, Chung Shan Medical University, Taichung, Taiwan

Correspondence to:

Jiunn-Liang Ko, e-mail: jlko@csmu.edu.tw

Po-Hui Wang, e-mail: wang082160@yahoo.com.tw

Keywords: voltage-dependent anion channel 1, gene silencing, cell growth, mitochondrial membrane potential, uterine cervical cancer

Received: June 23, 2015     Accepted: November 29, 2015     Published: December 21, 2015

ABSTRACT

Two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometry were performed to investigate the influence of human nonmetastatic clone 23 type 1 (nm23-H1), a metastasis-associated gene on proteomic alterations in cancer cells of the uterine cervix. It was validated by RT-PCR and Western blot analysis. The expression of voltage-dependent anion channel 1 (VDAC1) was increased in nm23-H1 gene silenced SiHa or CaSki cervical cancer cells. The clinical implication was shown that cervical cancer tissues with positive VDAC1 immunoreactivity exhibited deep stromal invasion (>10 mm in depth) and large tumor size (> 4 cm in diameter). Cervical cancer patients with positive VDAC1 immunoreactivity displayed higher recurrence and poorer overall survival than those with negative VDAC1. Silencing of VDAC1 reduced cell proliferation and migratory ability. Mitochondrial membrane potential was decreased and reactive oxygen species generation was increased in the VDAC1 gene-silenced cervical cancer cells. Cell cycle progression and autophagy were not changed in VDAC1 silencing cells. The cytotoxicity of cisplatin was significantly enhanced by knockdown of cellular VDAC1 and the compounds that interfere with hexokinase binding to VDAC. Therapeutic strategies may be offered using VDAC1 as a target to reduce cell growth and migration, enhance the synergistic therapeutic efficacy of cisplatin and reduce cisplatin dose-limiting toxicity.


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