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敲低长链非编码 RNA H19 通过触发细胞凋亡和调节 Akt 信号通路恢复紫杉醇耐药三阴性乳腺癌的化疗敏感性。

Knockdown of lncRNA H19 restores chemo-sensitivity in paclitaxel-resistant triple-negative breast cancer through triggering apoptosis and regulating Akt signaling pathway.

机构信息

Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, PR China.

Department of Internal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, PR China.

出版信息

Toxicol Appl Pharmacol. 2018 Nov 15;359:55-61. doi: 10.1016/j.taap.2018.09.018. Epub 2018 Sep 20.

Abstract

Triple negative breast cancer (TNBC) is associated with poor prognosis and systemic chemotherapy is the only treatment for TNBC. However, development of chemo-resistance remains a major obstacle for TNBC treatment. Paclitaxel-resistance is mainly related to the activation of the Akt signaling pathway and deregulation of apoptotic regulatory proteins. LncRNAs are frequently dysregulated in various malignancies, including breast cancer, facilitating cell proliferation, metastasis and drug resistance. LncRNA H19 is overexpressed in approximately 70% of breast cancer patients, and has been reported to confer chemo-resistance in breast cancer. In the present study, we investigated the expression level of lncRNA H19 in paclitaxel-resistant and paclitaxel-sensitive cell lines. The results showed that the level of lncRNA H19 expression in paclitaxel-resistant cells was significantly higher than that in paclitaxel-sensitive cells, and knockdown of lncRNA H19 might restore chemo-sensitivity in paclitaxel-resistant TNBC by mediating the AKT signaling pathway. Thus, lncRNA H19 might be an efficient therapeutic target in paclitaxel-resistant TNBC treatment.

摘要

三阴性乳腺癌(TNBC)与预后不良相关,全身化疗是 TNBC 的唯一治疗方法。然而,化疗耐药的发展仍然是 TNBC 治疗的主要障碍。紫杉醇耐药主要与 Akt 信号通路的激活和凋亡调节蛋白的失调有关。lncRNAs 在各种恶性肿瘤中经常失调,包括乳腺癌,促进细胞增殖、转移和耐药性。lncRNA H19 在大约 70%的乳腺癌患者中过表达,并被报道在乳腺癌中赋予化疗耐药性。在本研究中,我们研究了 lncRNA H19 在紫杉醇耐药和紫杉醇敏感细胞系中的表达水平。结果表明,紫杉醇耐药细胞中 lncRNA H19 的表达水平明显高于紫杉醇敏感细胞,lncRNA H19 的敲低可能通过调节 AKT 信号通路恢复紫杉醇耐药性 TNBC 的化疗敏感性。因此,lncRNA H19 可能是紫杉醇耐药性 TNBC 治疗的有效治疗靶点。

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