title: Effect of LIV1 on the sensitivity of ovarian cancer cells to trichostatin A.
abstract: In a previous study, we used a functional gene screen approach to identify the key genes responsible for the tumor-selective action of trichostatin A (TSA), of which LIV1, a novel zinc transporter, was isolated by its marked ability to confer resistance against TSA-induced apoptosis. The aim of the present study was to investigate the effect of LIV1 expression on the sensitivity of ovarian cancer cells to TSA. We tested the induction of LIV1 in ovarian cancer cells and clinical samples after TSA treatment by real-time PCR and western blot analysis. We investigated the effect of LIV1 expression on the sensitivity of ovarian cancer cells to TSA by MTT assay, flow cytometry and colony forming assays. Finally, we analyzed the mechanism of LIV1 in ovarian cancer cells by western blot analysis. We found that the levels of LIV1 mRNA and protein were significantly upregulated after TSA treatment. The viability and colony forming rates of the ovarian cancer cells transfected with AS-LIV1 (pCEP4 carrying antisense LIV1 cDNA) were obviously higher than the rates of the control as detected by MTT and colony forming assays, which could be reversed by FL-LIV1 (pCEP4 carrying full-length LIV1 cDNA). The apoptotic rate of the AS-LIV1 cells was markedly lower than the rate of the control as determined FACS. Using western blot analysis, we demostrated that the inhibition of TSA-induced apoptosis by knockdown of LIV1 might be associated with decreased endogenous levels of Bcl-2, enhanced levels of Bax and cleavage of procaspase-3. The present study suggests that the drug resistance of ovarian cancer cells to TSA may be related to expression of the LIV1 gene, and targeting LIV1 could be exploited as a novel strategy to more effectively kill ovarian cancer cells.
authors.affiliation: Gynecological Minimal Invasive Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100006, P.R. China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ma
authors.affiliation: Gynecological Minimal Invasive Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100006, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Duan
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Mo
authors.affiliation: Gynecological Minimal Invasive Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100006, P.R. China.
authors.forename: Chengjuan
authors.initials: C
authors.lastname: Sun
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Ding
authors.initials: D
authors.lastname: Ma
authors.affiliation: Gynecological Minimal Invasive Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100006, P.R. China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry*; D009363:Neoplasm Proteins / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D010051:Ovarian Neoplasms / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C000595707:BCL2 protein, human; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D006877:Hydroxamic Acids; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C418627:SLC39A6 protein, human; C017800:zinc-binding protein; C012589:trichostatin A