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洛铂对体外和体内 Ishikawa 子宫内膜癌细胞的抗肿瘤作用。

The antitumor effect of lobaplatin against Ishikawa endometrial cancer cells in vitro and in vivo.

机构信息

Department of Oncology, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao, Nanjing 210009, China.

Department of Oncology, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao, Nanjing 210009, China.

出版信息

Biomed Pharmacother. 2019 Jun;114:108762. doi: 10.1016/j.biopha.2019.108762. Epub 2019 Mar 27.

Abstract

The new effective chemotherapeutic drugs are required urgently for advanced and recurrent endometrial carcinoma (EC), which is one of the most common gynaecological tumors among women worldwide. Preclinical studies have shown that lobaplatin, one of the third-generation platinum compounds, has possessed powerful anti-cancer efficacy on a series of tumors. The purpose of this study is to investigate its effect and molecular mechanism on the growth of endometrial cancer cell line Ishikawa in vitro and in vivo. The results of cell counting kit-8 (CCK-8) shown that lobaplatin concentration-dependent inhibited cell proliferations in human endometrial carcinoma ishikawa cells. Flow cytometry (FCM) assay demonstrated that lobaplatin affected the survival of endometrial carcinoma cell by arresting cell cycle at S phase and G2/M phase and inducing apoptosis in dose-dependent manner. Moreover, Western blot analysis also showed that the apoptosis-inducing effects of lobaplatin was associated with the reduction of Bcl-2 expression while upregulation of cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9 and Bax. Meanwhile, lobaplatin significantly suppressed tumor growth of human Ishikawa xenograft models and terminal deoxynucleotidyl trans-ferase dUTP nick end labeling confirmed the significant occurrence of lobaplatin-treated tumor tissues of apoptosis. Therefore, lobaplatin could be an effective chemotherapeutic agent for human endometrial carcinoma and warrants further clinical investigation.

摘要

新的有效化疗药物对于晚期和复发性子宫内膜癌(EC)是急需的,EC 是全世界女性最常见的妇科肿瘤之一。临床前研究表明,第三代铂类化合物之一洛铂对一系列肿瘤具有强大的抗癌作用。本研究旨在探讨洛铂对体外和体内子宫内膜癌细胞系 Ishikawa 生长的作用及其分子机制。细胞计数试剂盒(CCK-8)的结果表明,洛铂浓度依赖性抑制人子宫内膜癌 ishikawa 细胞的增殖。流式细胞术(FCM)检测表明,洛铂通过将细胞周期阻滞在 S 期和 G2/M 期以及剂量依赖性诱导细胞凋亡来影响子宫内膜癌细胞的存活。此外,Western blot 分析还表明,洛铂的诱导细胞凋亡作用与 Bcl-2 表达的降低有关,而 cleaved-caspase-3、cleaved-caspase-8、cleaved-caspase-9 和 Bax 的上调有关。同时,洛铂显著抑制人 Ishikawa 异种移植模型的肿瘤生长,末端脱氧核苷酸转移酶 dUTP 缺口末端标记证实了洛铂处理的肿瘤组织中凋亡的显著发生。因此,洛铂可能是一种有效的治疗人类子宫内膜癌的化疗药物,值得进一步的临床研究。

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