Oncotarget

Research Papers:

Synthetic paclitaxel-octreotide conjugate reversing the resistance of A2780/Taxol to paclitaxel in xenografted tumor in nude mice

Xi Chen _, Xiao-Yu Zhang, Yang Shen, Li-Li Fan, Mu-Lan Ren and Yong-Ping Wu

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Oncotarget. 2016; 7:83451-83461. https://doi.org/10.18632/oncotarget.13120

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Abstract

Xi Chen1, Xiao-Yu Zhang1, Yang Shen1, Li-Li Fan1, Mu-Lan Ren1, Yong-Ping Wu2

1Department of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China

2Jiangsu Provincial Institute of Materia Medica, Nanjing 210009, China

Correspondence to:

Yang Shen, email: shenyang0924@sina.cn

Keywords: ovarian cancer, paclitaxel, somatostatin, conjugate, resistance

Received: July 22, 2016     Accepted: October 12, 2016     Published: November 04, 2016

ABSTRACT

Peptide hormone-based targeted therapy to tumors has been studied extensively. Our previous study shows that somatostatin receptor expresses high level on drug-resistant human ovarian cancer. The paclitaxel-octreotide conjugate (POC) exhibits enhanced growth inhibition, as well as reduced toxicity, in paclitaxel-resistant human ovarian cancer cells. The aim of this study was to investigate the effect of targeted cytotoxicity and potential reversal mechanism of resistance in paclitaxel-resistant human ovarian cancer cells xenografted into nude mice. The SSTR2 shows higher expression levels in tumor tissue. Moreover, fluorescein-labeled POC displays favorable targeting in tumor cells. POC presents the perfect efficacy in inhibiting tumor growth and exerts lower or no toxic effects on normal tissues. Real-time PCR and Western Blotting has demonstrated that the mRNA and protein expressions of SSTR2 in POC group were significantly higher, while MDR1, α-tubulin, βIII-tubulin, VEGF and MMP-9 were significantly lower than in the other treatment groups and controls. Combined with the previous study in vitro, this study evaluates an effective approach on the treatment of paclitaxel-resistant ovarian cancer which expresses somatostatin receptor SSTR. Our investigation has also revealed the possible molecular mechanism of POC in treating the ovarian cancer, and therefore, provided a theoretical basis for the clinical application of this newly-invented compound.


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