title: Clinical implication of voltage-dependent anion channel 1 in uterine cervical cancer and its action on cervical cancer cells.
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.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chih-Hsien
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Lin
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Tzu-Fan
authors.initials: TF
authors.lastname: Wu
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Jiunn-Liang
authors.initials: JL
authors.lastname: Ko
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.|Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan.|School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Po-Hui
authors.initials: PH
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D053078:Membrane Potential, Mitochondrial; D054778:NM23 Nucleoside Diphosphate Kinases / Q000378:metabolism; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D050995:Voltage-Dependent Anion Channel 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D054778:NM23 Nucleoside Diphosphate Kinases; D012333:RNA, Messenger; C494762:VDAC1 protein, human; D050995:Voltage-Dependent Anion Channel 1
keywords: cell growth; gene silencing; mitochondrial membrane potential; uterine cervical cancer; voltage-dependent anion channel 1