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热休克蛋白27(HSP27)在结肠癌细胞多药敏感性和耐药性中的作用。

Role of HSP27 in the multidrug sensitivity and resistance of colon cancer cells.

作者信息

Liu Zhengyong, Liu Yi, Long Yupeng, Liu Baohua, Wang Xiangfeng

机构信息

Department of General Surgery, Daping Hospital, Army Medical University, Chongqing 400042, P.R. China.

Department of Information, Daping Hospital, Army Medical University, Chongqing 400042, P.R. China.

出版信息

Oncol Lett. 2020 Mar;19(3):2021-2027. doi: 10.3892/ol.2020.11255. Epub 2020 Jan 7.

Abstract

Multidrug resistance in cancer cells is a primary factor affecting therapeutic efficacy. Heat shock 27 kD protein 1 (HSP27) is associated with cell apoptosis and resistance to chemotherapy. However, the mechanisms underlying HSP27-associated pathways in colon cancer cells remain unclear. Therefore, the present study used short hairpin (sh) RNA to inhibit HSP27 expression in colon cancer cells in order to investigate the effects and . Flow cytometry was used to investigate cell apoptosis and a xenograft model was employed to examine the tumorigenesis. Protein expression was measured by Western blotting. The results revealed that suppression of HSP27 expression significantly increased cell apoptosis, inhibited tumor growth and enhanced sensitivity to the anti-cancer agents 5-fluorouracil (5-FU) and vincristine (VCR). shHSP27 significantly decreased the expression of notch receptor 1 and the phosphorylation level of Akt and mTOR, and enhanced the effect of 5-FU and VCR. In conclusion, HSP27 suppression enhanced the sensitivity of colon cancer cells to 5-FU and VCR, and increased colon cancer cell apoptosis with and without chemotherapy. Therefore, the development of novel therapeutic agents that inhibit the expression of HSP27 may offer a new treatment option for colon cancer.

摘要

癌细胞中的多药耐药性是影响治疗效果的主要因素。热休克27kD蛋白1(HSP27)与细胞凋亡和化疗耐药性相关。然而,结肠癌细胞中HSP27相关通路的潜在机制仍不清楚。因此,本研究使用短发夹(sh)RNA抑制结肠癌细胞中HSP27的表达,以研究其影响。采用流式细胞术检测细胞凋亡,并采用异种移植模型检测肿瘤发生情况。通过蛋白质印迹法检测蛋白质表达。结果显示,抑制HSP27表达可显著增加细胞凋亡,抑制肿瘤生长,并增强对抗癌药物5-氟尿嘧啶(5-FU)和长春新碱(VCR)的敏感性。shHSP27显著降低Notch受体1的表达以及Akt和mTOR的磷酸化水平,并增强5-FU和VCR的作用。总之,抑制HSP27可增强结肠癌细胞对5-FU和VCR的敏感性,并在有无化疗的情况下增加结肠癌细胞凋亡。因此,开发抑制HSP27表达的新型治疗药物可能为结肠癌提供一种新的治疗选择。

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