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GPSM2的下调与乳腺癌对紫杉醇的原发性耐药相关。

Downregulation of GPSM2 is associated with primary resistance to paclitaxel in breast cancer.

作者信息

Zhang Zhe, Li Zhi, Deng Mingming, Liu Bofang, Xin Xing, Zhao Zhenkun, Zhang Ye, Lv Qingjie

机构信息

Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.

Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.

出版信息

Oncol Rep. 2020 Mar;43(3):965-974. doi: 10.3892/or.2020.7471. Epub 2020 Jan 17.

Abstract

Paclitaxel is one of the most effective chemotherapy drugs for breast cancer worldwide but 20‑30% patients show primary resistance to the drug. Screening and identification of markers that facilitate effective and rapid prediction of sensitivity to paclitaxel is therefore an urgent medical requirement. In the present study, G protein signaling modulator 2 (GPSM2) mRNA levels were significantly associated with taxane sensitivity in experiments based on the Gene Expression Omnibus (GEO) online database. Immunohistochemical analysis consistently revealed a significant association of GPSM2 protein levels with paclitaxel sensitivity in breast cancer patients. Knockdown of GPSM2 reduced the sensitivity of breast cancer cells to paclitaxel via regulation of the cell cycle. Animal experiments further corroborated our in vitro findings. These results suggest that GPSM2 plays an important role in breast cancer resistance, supporting its utility as a potential target for improving drug susceptibility in patients as well as a marker of paclitaxel sensitivity.

摘要

紫杉醇是全球范围内治疗乳腺癌最有效的化疗药物之一,但20%-30%的患者对该药物表现出原发性耐药。因此,筛选和鉴定有助于有效、快速预测紫杉醇敏感性的标志物是一项迫切的医学需求。在本研究中,基于基因表达综合数据库(GEO)在线数据库的实验表明,G蛋白信号调节剂2(GPSM2)的mRNA水平与紫杉烷敏感性显著相关。免疫组织化学分析一致显示,乳腺癌患者中GPSM2蛋白水平与紫杉醇敏感性显著相关。敲低GPSM2可通过调节细胞周期降低乳腺癌细胞对紫杉醇的敏感性。动物实验进一步证实了我们的体外研究结果。这些结果表明,GPSM2在乳腺癌耐药中起重要作用,支持其作为改善患者药物敏感性的潜在靶点以及紫杉醇敏感性标志物的效用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed96/7041173/bb9bad86c9c8/OR-43-03-0965-g00.jpg

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