Therapeutic Effect of Glypican-3 Gene Silencing Using siRNA for Ovarian Cancer in a Murine Peritoneal Dissemination Model

M. Hazekawa, T. Nishinakagawa, Tomoyo Kawakubo-Yasukochi, M. Nakashima
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Abstract

Ovarian cancer is known to be the most lethal gynecologic cancer. It has been reported that Glypican-3 (Gpc3) expression induces immune responses, promotes the progression in ovarian cancer. Then, we focused on this Gpc3 gene silencing, tried to prepare siRNA delivery system. In this chapter, we introduce one of the therapeutic proposals in terms of novel drug delivery system using siRNA as a targeting medicine. This chapter introduces our works about preparation of siRNA-PLGA hybrid micelles to deliver the siRNA into the ovarian cancer cells and to evaluate gene silencing effects in mice model. As a result, siRNA-PLGA hybrid micelles were shown to effectively inhibit Gpc3 expression in vitro . In addition, siRNA-PLGA hybrid micelles also decreased the number of tumor nodes in the mesentery in vivo. These results suggested that Gpc3 could be a target molecule for ovarian cancer treatment and siRNA-PLGA hybrid micelles could be an effective siRNA delivery tool even in vivo .
使用siRNA沉默Glypican-3基因对小鼠腹腔播散模型卵巢癌的治疗作用
卵巢癌被认为是最致命的妇科癌症。据报道,Glypican-3 (Gpc3)表达可诱导免疫应答,促进卵巢癌的进展。然后,我们针对这种Gpc3基因的沉默,尝试制备siRNA的递送系统。在本章中,我们介绍了利用siRNA作为靶向药物的新型药物传递系统的治疗建议之一。本章介绍了我们制备siRNA- plga杂交胶束,将siRNA传递到卵巢癌细胞并在小鼠模型上评估基因沉默效果的工作。结果表明,siRNA-PLGA杂交胶束在体外有效抑制Gpc3的表达。此外,siRNA-PLGA杂交胶束在体内也减少了肠系膜内肿瘤淋巴结的数量。这些结果表明Gpc3可能是卵巢癌治疗的靶分子,siRNA- plga杂交胶束在体内也可能是一种有效的siRNA递送工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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