title: Synergistic antitumor activities of docetaxel and octreotide associated with apoptotic-upregulation in castration-resistant prostate cancer.
abstract: Androgen deprivation therapy has become the fist-line treatment of metastatic prostate cancer; however, progression to castrate resistance disease occurs in the majority of patients. Thus, there is an urgent need for improvements in therapy for castration-resistant prostate cancer. The aims of the present study were to determine the efficacy somatostatin analogue octreotide (OCT) combined with a low dose of docetaxel (DTX) using castration resistant prostate cancer cells and to investigate the involved molecular mechanisms in vitro. The anti-proliferative and synergism potential effects were determined by MTT assay. Induction of apoptosis was analyzed employing annexing V and propidium iodide staining and flow cytometry. VEGFA, CASP9, CASP3 and ABCB1 gene expression was evaluated by RT-PCR and Q-RT-PCR analysis. OCT in combination with DTX treatments on DU145 cell migration was also evaluated. Investigation revealed that combined administration of DTX and OCT had significant, synergistically greater cytotoxicity than DTX or OCT treatment alone. The combination of the two drugs caused a more marked increase in apoptosis and resulted in greater suppression of invasive potential than either individual agent. There was obvious increase in caspase 3 expression in the OCT alone and two-drug combined treatment groups, however, VEGFA expression was markedly suppressed in them. These results support the conclusion that somatostatin analogues combined with docetaxel may enhance the chemotherapy efficacies through multiple mechanisms in castration-resistant PCa cell line. This work provides a preclinical rationale for the therapeutic strategies to improve the treatment in castrate resistance disease.
authors.affiliation: Department of Microbiology and Immunology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, P. R. China.
authors.forename: Sha
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Microbiology and Immunology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, P. R. China.
authors.forename: Judith Apondi
authors.initials: JA
authors.lastname: Oremo
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College, Henan University of Science and Technology, Luoyang, P. R. China.
authors.forename: Sanqiang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Microbiology and Immunology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, P. R. China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Zhen
authors.affiliation: Department of Microbiology and Immunology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, P. R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Microbiology and Immunology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, P. R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Du
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004357:Drug Synergism; D006801:Humans; D008297:Male; D015282:Octreotide / Q000494:pharmacology*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D012333:RNA, Messenger; D043823:Taxoids; D042461:Vascular Endothelial Growth Factor A; D000077143:Docetaxel; D053148:Caspase 3; D053453:Caspase 9; D015282:Octreotide