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选择性生存素抑制剂YM155与顺铂联合应用于肝母细胞瘤的抗肿瘤活性

Antitumor activity of YM155, a selective survivin suppressant, in combination with cisplatin in hepatoblastoma.

作者信息

Yu Ying, Zhao Xiaosu, Zhang Yu, Kang Yanling, Wang Jiaqi, Liu Yingchun

机构信息

Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.

The Nursing Department of the First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.

出版信息

Oncol Rep. 2015 Jul;34(1):407-14. doi: 10.3892/or.2015.3947. Epub 2015 May 5.

Abstract

Cisplatin (CDDP) is a chemotherapeutic drug that is often used for the treatment of hepatoblastoma. However, many patients acquire resistance to therapeutic agents leading to local and distant treatment failure. It has been shown that suppression survivin contributed to the inhibition of tumor growth and enhanced chemotherapeutic sensitivity in several types of cancer. The aim of the present study was to determine whether treatment with sepantronium bromide (YM155), a novel small molecule inhibitor of survivin, enhanced the sensitivity of CDDP to hepatoblastoma cells, leading to the therapeutic efficacy of cisplatin. In vitro and in vivo models were used to examine the anticancer efficacy of YM155, either as a monotherapy or in combination with CDDP to identify more effective therapeutics against hepatoblastoma. The results showed that survivin expression was upregulated in hepatoblastoma tissues and cell lines, and that YM155 inhibited survivin expression in hepatoblastoma cells in a dose-dependent manner. YM155 enhanced sensitivity of CDDP to human HepG2 and HuH-6 hepatoblastoma cells. The YM155 combination with CDDP in hepatoblastoma cells significantly decreased cell proliferation and formation, and induced cell apoptosis than either agent alone. In a mouse xenograft model, YM155 combined with CDDP significantly suppressed tumor growth compared to the monotherapy. Taken together, these findings suggested that the combination of YM155 and CDDP is a promising drug candidate for the treatment of hepatoblastoma.

摘要

顺铂(CDDP)是一种常用于治疗肝母细胞瘤的化疗药物。然而,许多患者会对治疗药物产生耐药性,导致局部和远处治疗失败。研究表明,抑制生存素有助于抑制多种癌症的肿瘤生长并增强化疗敏感性。本研究的目的是确定新型小分子生存素抑制剂司帕沙星(YM155)治疗是否能增强顺铂对肝母细胞瘤细胞的敏感性,从而提高顺铂的治疗效果。使用体外和体内模型来研究YM155作为单一疗法或与顺铂联合使用时的抗癌效果,以确定更有效的肝母细胞瘤治疗方法。结果表明,生存素在肝母细胞瘤组织和细胞系中表达上调,且YM155以剂量依赖方式抑制肝母细胞瘤细胞中的生存素表达。YM155增强了顺铂对人HepG2和HuH-6肝母细胞瘤细胞的敏感性。与单独使用任何一种药物相比,YM155与顺铂联合使用可显著降低肝母细胞瘤细胞的增殖和形成,并诱导细胞凋亡。在小鼠异种移植模型中,与单一疗法相比,YM155与顺铂联合使用可显著抑制肿瘤生长。综上所述,这些发现表明YM155与顺铂联合使用是治疗肝母细胞瘤的一种有前景的候选药物。

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