Synthetic paclitaxel-octreotide conjugate reverses the resistance of paclitaxel in A2780/Taxol ovarian cancer cell line

Shen,Yang; Zhang,Xiao-Yu; Chen,Xi; Fan,Li-Li; Ren,Mu-Lan; Wu,Yong-Ping; Chanda,Kenneth; Jiang,Shi-Wen

doi:10.3892/or.2016.5260

Synthetic paclitaxel-octreotide conjugate reverses the resistance of paclitaxel in A2780/Taxol ovarian cancer cell line

Authors:
- Yang Shen
- Xiao-Yu Zhang
- Xi Chen
- Li-Li Fan
- Mu-Lan Ren
- Yong-Ping Wu
- Kenneth Chanda
- Shi-Wen Jiang
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Affiliations: Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China, Jiangsu Provincial Institute of Materia Medica, Nanjing, Jiangsu 210009, P.R. China, Department of Obstetrics and Gynecology, University of Zambia, University Teaching Hospital, Lusaka, Zambia, Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China
Published online on: November 18, 2016 https://doi.org/10.3892/or.2016.5260
Pages: 219-226

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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.

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