title: Synthetic paclitaxel-octreotide conjugate reverses the resistance of paclitaxel in A2780/Taxol ovarian cancer cell line.
abstract: The high mortality of ovarian cancer is partly due to the frequent resistance of ovarian cancer to current chemotherapy agents such as paclitaxel and platinum. Somatostatin analogue (SSTA) has been shown to inhibit the proliferation of some tumors through binding to somatostatin receptor (SSTR) and activation of Ras-, Rapl- and B-Raf-dependent extracellular signal-regulated kinase 2 (Erk2). It was reported that paclitaxel-octreotide conjugate (POC) exhibited enhanced tumor growth inhibition with reduced toxicity. In the present study, we prepared the POC and investigated its effects and mechanism for the reversal of drug resistance in paclitaxel-resistant ovarian cancer cell line. We demonstrated that treatment with POC led to more cell apoptosis than either paclitaxel or octreotide (OCT) alone. Moreover, the expression of multidrug resistance 1 (MDR1) and vascular endothelial growth factor (VEGF) mRNA, and protein decreased in a dose-dependent manner while the expression of SSTR remained stable following treatment with POC. Although the exact action, in vivo effects and pharmacologic kinetics of POC remain to be investigated, we have demonstrated the feasibility for the synthesis of POC, and more significantly, provided a potential approach to overcome the resistance of ovarian cancer against taxol. The findings also shed some new light on the mechanisms underlying the development of resistance to taxol by ovarian cancer cells.
authors.affiliation: Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Fan
authors.affiliation: Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Mu-Lan
authors.initials: ML
authors.lastname: Ren
authors.affiliation: Jiangsu Provincial Institute of Materia Medica, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynecology, University of Zambia, University Teaching Hospital, Lusaka, Zambia.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Chanda
authors.affiliation: Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China.
authors.forename: Shi-Wen
authors.initials: SW
authors.lastname: Jiang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015282:Octreotide / Q000737:chemistry / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology*; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D004338:Drug Combinations; D017481:Receptors, Somatostatin; C574734:SSTR2 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017239:Paclitaxel; D015282:Octreotide