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BRCA1 野生型三阴性乳腺癌细胞在吉西他滨和聚(ADP-核糖)聚合酶-1 抑制剂联合治疗后 miR-206 表达降低。

Decreased miR-206 expression in BRCA1 wild-type triple-negative breast cancer cells after concomitant treatment with gemcitabine and a Poly(ADP-ribose) polymerase-1 inhibitor.

机构信息

Department of Pharmacology, School of Medicine, Showa University, Shinagawa-ku, Tokyo, Japan

Kameda Medical Center, Breast Center, Kamogawa City, Chiba, Japan.

出版信息

Anticancer Res. 2014 Sep;34(9):4893-7.

Abstract

No targeted-therapy has been established for triple-negative breast cancer accompanied by mutations in breast cancer susceptibility gene1 (BRCA1) mutation. In the present study, using BRCA1 wild-type cells (MDA-MB-231) and BRCA1-mutated cells (MDA-MB-436), we investigated miRNA expression and apoptosis on day 1 after addition of gemcitabine-alone and in combination with poly ADP-ribose polymerase-1 (PARP1) inhibitor. After drug treatment, there were significantly fewer apoptotic BRCA1 wild-type cells than BRCA1-mutated cells. Expression of miRNA-26a, -29b, -100, and -148a increased in BRCA1 wild-type cells exposed to gemcitabine-alone and in combination with the PARP1 inhibitor. The addition of PARP1 inhibitor reduced miR-206 expression in BRCA1 wild-type cells but increased it in BRCA1-mutated cells. It was suggested that miR-206 serves as a target molecule of PARP1 inhibitor combination therapy for BRCA1 wild-type triple-negative breast cancer cells.

摘要

对于同时伴有乳腺癌易感基因 1 (BRCA1) 突变的三阴性乳腺癌,目前尚无靶向治疗方法。本研究采用 BRCA1 野生型细胞(MDA-MB-231)和 BRCA1 突变型细胞(MDA-MB-436),研究了吉西他滨单药及与聚 ADP-核糖聚合酶-1(PARP1)抑制剂联合应用后第 1 天的 miRNA 表达和细胞凋亡情况。药物处理后,BRCA1 野生型细胞的凋亡明显少于 BRCA1 突变型细胞。暴露于吉西他滨单药及与 PARP1 抑制剂联合应用的 BRCA1 野生型细胞中,miRNA-26a、-29b、-100 和 -148a 的表达增加。PARP1 抑制剂的添加降低了 BRCA1 野生型细胞中 miR-206 的表达,但增加了 BRCA1 突变型细胞中 miR-206 的表达。提示 miR-206 可能是 BRCA1 野生型三阴性乳腺癌细胞 PARP1 抑制剂联合治疗的靶分子。

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