Restoration of the ATG5-dependent autophagy sensitizes DU145 prostate cancer cells to chemotherapeutic drugs.

Restoration of the ATG5-dependent autophagy sensitizes DU145 prostate cancer cells to chemotherapeutic drugs.
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ATG5 依赖性自噬的恢复使 DU145 前列腺癌细胞对化疗药物敏感。

DOI:
10.3892/ol.2021.12899
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发表时间:
2021-09
期刊:
影响因子:
2.9
通讯作者:
Lin Q
Lin Q
中科院分区:
医学4区
文献类型:
--
作者:
Peng K;Sun A;Zhu J;Gao J;Li Y;Shao G;Yang W;Lin Q

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自噬在癌细胞存活和耐药性中起重要作用。在本研究中,使用前列腺癌DU 145细胞系,其缺乏自噬相关5(ATG 5)表达并且在诱导ATG 5依赖性自噬方面有缺陷。该研究的目的是检查自噬恢复对细胞增殖和迁移的影响,并使用显微镜、伤口愈合、蛋白质印迹和凋亡测定来评估化疗药物引起的细胞毒性。通过过表达ATG 5恢复DU 145细胞中的自噬活性,增强细胞增殖和迁移速率。值得注意的是,在DU 145细胞中恢复ATG 5依赖性自噬显著增加了化疗药物多西他赛和丙戊酸以及内质网应激诱导剂布雷菲德菌素A、衣霉素和毒胡萝卜素的细胞毒性作用。本研究为ATG5依赖性自噬在耐药和化疗中的作用提供了新的视角。
Autophagy serves an important role in cancer cell survival and drug resistance. In the present study, the prostate cancer DU145 cell line was used, which lacks autophagy related 5 (ATG5) expression and is defective in induction of ATG5-dependent autophagy. The aim of the study was to examine the effects of the restoration of autophagy on cell proliferation and migration, and to assess the cytotoxicity caused by chemotherapeutic drugs, using microscopic, wound-healing, western blot and apoptotic assays. The restoration of the autophagic activity in DU145 cells by the overexpression of ATG5 enhanced the cell proliferation and migration rates. Notably, restoration of the ATG5-dependent autophagy in DU145 cells significantly increased the cytotoxic effects of the chemotherapeutic drugs, docetaxel and valproic acid, and the endoplasmic reticulum stress inducers, brefeldin A, tunicamycin and thapsigargin. The present study provides a novel perspective on the role of ATG5-dependent autophagy in drug resistance and chemotherapy.
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