title: The combinatory effects of PPAR-γ agonist and survivin inhibition on the cancer stem-like phenotype and cell proliferation in bladder cancer cells.
abstract: Strategies for peroxisome proliferator-activated receptor (PPAR) activation or survivin inhibition have potential for cancer therapy. However, whether the combination of these two approaches can be developed as a rational regimen with enhanced efficiency in the inhibition of tumor cells remains to be determined. In this study, the combinatory effect of PPAR-γ agonist and survivin inhibition on bladder cancer cells was investigated. T24 and 5637 cells were treated with 15d-PGJ(2) to determine whether 15d-PGJ(2) had an inhibitory effect. Cell viability and proliferation were analyzed and efficiency of survivin siRNAs was assessed using western blot analysis. The results showed that, in the human bladder cancer cell lines T24 and 5637, the natural PPAR-γ ligand 15d-PGJ(2) significantly decreased cell proliferation and loci formation. The increase in the proportion of apoptotic cells was observed in the cells 48 h after 15d-PGJ(2) treatment. Furthermore, 15d-PGJ(2) substantially inhibited the levels of stemness-related genes in these cells. The ability of sphere formation was markedly suppressed in the cells treated with 15d-PGJ(2). More importantly, the downregulation of survivin with siRNAs significantly enhanced the 15d-PGJ(2)-mediated induction of cell apoptosis and inhibition of sphere formation. Accordingly, we also found that survivin inhibition significantly enhanced 15d-PGJ(2)-induced production of reactive oxygen species (ROS) in bladder cancer cells. Taken together, these findings suggest that the combination of 15d-PGJ(2) and survivin inhibition play a potentially role in the therapeutical manipulation of bladder cancer.
authors.affiliation: Department of Urology, Shanghai No. 5 People's Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Urology, Shanghai No. 5 People's Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Tan
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Renji Hospital, Shanghai Cancer Institute, Shanghai, P.R. China.
authors.forename: Dongxu
authors.initials: D
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Renji Hospital, Shanghai Cancer Institute, Shanghai, P.R. China.
authors.forename: Aihui
authors.initials: A
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Renji Hospital, Shanghai Cancer Institute, Shanghai, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Renji Hospital, Shanghai Cancer Institute, Shanghai, P.R. China.
authors.forename: Jiabin
authors.initials: J
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Renji Hospital, Shanghai Cancer Institute, Shanghai, P.R. China.
authors.forename: Zhaojuan
authors.initials: Z
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Renji Hospital, Shanghai Cancer Institute, Shanghai, P.R. China.
authors.forename: Yongzhong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Urology, Shanghai No. 5 People's Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Guowei
authors.initials: G
authors.lastname: Shi
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D047495:PPAR gamma / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism; D015398:Signal Transduction; D000077022:Survivin; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: C477819:15-deoxyprostaglandin J2; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D047495:PPAR gamma; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D000077022:Survivin; D015230:Prostaglandin D2