Department of General Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Department of Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Bioengineered. 2020 Dec;11(1):472-483. doi: 10.1080/21655979.2020.1747825.
Recent focus has turned to secretory clusterin (sCLU) as a key contributor to chemoresistance of anticancer agents, but the role of sCLU on chemotherapy drug response to gastric cancer cells is not fully understood. Previous research found that sCLU was overexpressed in the induced multidrug-resistant MGC-803/5-FU cell line, suggesting that sCLU upregulation was closely related to chemoresistance to anticancer agents. In the present study, we aimed to clarify the role and mechanisms of sCLU in regulating the chemoresistance of gastric cancer cells. Cell apoptosis and cell viability were evaluated by annexin V/propidium iodide staining and CCK8. Expression of sCLU and miR-195-5P was detected using quantitative RT-PCR assays. The expression of sCLU in gastric cancer tissues was detected by RT-PCR assays. Upregulating or downregulating sCLU or miR-195-5P in gastric cancer cells was used to evaluate the mechanisms of chemoresistance. We found that sCLU was significantly elevated in the MGC-803/5-FU and SGC-7901 cells, and the downregulating sCLU sensitized MGC-803/5-FU and SGC-7901 cells to cisplatin and Docetaxel by upregulation of miR-195-5P. Upregulating sCLU in MGC-803 and HGC-27 cells was resistant to cisplatin and Docetaxel by downregulating miR-195-5p. Targeting miR-195-5P reduced the sensitivity of MGC-803 cells to 5-FU, and miR-195-5P overexpression enhanced the sensitivity of MGC-803/5-FU cells to 5-FU. The overexpression of sCLU in gastric cancer tissues was associated with chemoresistance. Our findings suggest that overexpression of sCLU induced chemoresistance in gastric cancer cells by downregulating miR-195-5p, thus providing a potential target for the development of agents that targeting sCLU for gastric cancer therapy.
最近的研究焦点集中在分泌型簇蛋白 (sCLU) 上，认为其是抗癌药物产生耐药性的关键因素，但 sCLU 对胃癌细胞化疗药物反应的作用尚未完全阐明。先前的研究发现 sCLU 在诱导的多药耐药 MGC-803/5-FU 细胞系中过表达，提示 sCLU 的上调与抗癌药物的耐药性密切相关。本研究旨在阐明 sCLU 在调节胃癌细胞耐药性中的作用及其机制。通过 Annexin V/碘化丙啶染色和 CCK8 评估细胞凋亡和细胞活力。采用定量 RT-PCR 检测 sCLU 和 miR-195-5P 的表达。采用 RT-PCR 检测胃癌组织中 sCLU 的表达。上调或下调胃癌细胞中的 sCLU 或 miR-195-5P 用于评估耐药性的机制。我们发现 sCLU 在 MGC-803/5-FU 和 SGC-7901 细胞中显著升高，下调 sCLU 通过上调 miR-195-5P 使 MGC-803/5-FU 和 SGC-7901 细胞对顺铂和多西他赛敏感。上调 MGC-803 和 HGC-27 细胞中的 sCLU 通过下调 miR-195-5p 对顺铂和多西他赛产生耐药性。靶向 miR-195-5P 降低了 MGC-803 细胞对 5-FU 的敏感性，而过表达 miR-195-5P 增强了 MGC-803/5-FU 细胞对 5-FU 的敏感性。胃癌组织中 sCLU 的过表达与化疗耐药性相关。我们的研究结果表明，sCLU 的过表达通过下调 miR-195-5p 诱导胃癌细胞产生耐药性，因此为开发针对 sCLU 的药物治疗胃癌提供了一个潜在的靶点。
