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PectaSol-C改性柑橘果胶(一种半乳糖凝集素-3抑制剂)与紫杉醇对人SKOV-3卵巢癌细胞凋亡的协同作用。

Synergistic effects of PectaSol-C modified citrus pectin an inhibitor of Galectin-3 and paclitaxel on apoptosis of human SKOV-3 ovarian cancer cells.

作者信息

Hossein Ghamartaj, Keshavarz Maryam, Ahmadi Samira, Naderi Nima

机构信息

Department of Animal Physiology, Developmental Biology Laboratory, School of Biology, University College of Science, University of Tehran, Tehran, Iran E-mail :

出版信息

Asian Pac J Cancer Prev. 2013;14(12):7561-8. doi: 10.7314/apjcp.2013.14.12.7561.

Abstract

Galectin-3 (Gal-3) is a carbohydrate-binding protein which is thought to be involved in cancer progression but its contribution to epithelial ovarian cancer (EOC) remains unclear. The present study sought to determine the role of Gal-3 in chemoresistance of the human SKOV-3 ovarian cancer cell line to paclitaxel (PTX) using recombinant human Gal-3 (rhGal-3) and PectaSol-C modified citrus pectin (Pect-MCP) as a specific Gal-3 competitive inhibitor. Our results showed 41% increased cell proliferation, 36% decreased caspase-3 activity and 33.6% increased substrate-dependent adhesion in the presence of rhGal-3 compared to the control case (p<0.001). Treatment of cells with a non-effective dose of PTX (100nM) and 0.1% Pect-MCP in combination revealed synergistic cytotoxic effects with 75% reduced cell viability and subsequent 3.9-fold increase in caspase-3 activity. Moreover, there was 39% decrease in substrate-dependent adhesion compared to control (p<0.001). These results suggest that inhibition of Gal-3 could be a useful therapeutic tool for combination therapy of ovarian cancer.

摘要

半乳糖凝集素-3(Gal-3)是一种碳水化合物结合蛋白,被认为与癌症进展有关,但其对上皮性卵巢癌(EOC)的作用仍不清楚。本研究旨在使用重组人Gal-3(rhGal-3)和果胶溶胶-C改性柑橘果胶(Pect-MCP)作为特异性Gal-3竞争性抑制剂,确定Gal-3在人SKOV-3卵巢癌细胞系对紫杉醇(PTX)的化疗耐药性中的作用。我们的结果显示,与对照情况相比,在存在rhGal-3的情况下,细胞增殖增加41%,半胱天冬酶-3活性降低36%,底物依赖性黏附增加33.6%(p<0.001)。用无效剂量的PTX(100nM)和0.1% Pect-MCP联合处理细胞,显示出协同细胞毒性作用,细胞活力降低75%,随后半胱天冬酶-3活性增加3.9倍。此外,与对照相比,底物依赖性黏附降低39%(p<0.001)。这些结果表明,抑制Gal-3可能是卵巢癌联合治疗的一种有用的治疗工具。

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