title: Docetaxel enhances apoptosis and G2/M cell cycle arrest by suppressing mitogen-activated protein kinase signaling in human renal clear cell carcinoma.
abstract: Tremendous efforts have been made in renal cell carcinoma (RCC) patients' research; however, clinical findings in patients have been disappointing. The aims of our study were to identify better or alternative therapeutic methods that can reverse chemotherapy resistance and to enhance sensitivity to docetaxel (DOX)-based chemotherapy drugs. We evaluated the anti-proliferative effect of DOX against RCC cells. DOX was found to suppress proliferation of RCC cells under in vitro and in vivo settings. Flow cytometric analysis revealed that DOX suppressed cell growth by induction of both apoptosis and G2/M cell cycle arrest in a dose-dependent manner. Various patterns of gene expression were observed by cluster analysis. In addition, based on network analysis using the ingenuity pathway analysis software, DOX was found to suppress phosphorylation of extracellular signal-regulated kinase 1/2 and p38, suggesting that the mitogen-activated protein kinase signaling pathway plays a vital role in the anti-proliferative effect of DOX against RCC.
authors.affiliation: Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: T D
authors.initials: TD
authors.lastname: Han
authors.affiliation: Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: D H
authors.initials: DH
authors.lastname: Shang
authors.affiliation: Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Tian
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D043823:Taxoids / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases