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.

中文翻译：

---

分泌簇蛋白（sCLU）的过表达通过靶向miR-195-5p诱导人胃癌细胞的化疗耐药性。

最近的焦点已经转向分泌型簇蛋白（sCLU）作为抗癌剂化学耐药性的关键贡献者，但是尚未完全了解sCLU在化学疗法对胃癌细胞应答中的作用。先前的研究发现，sCLU在诱导的多药耐药性MGC-803 / 5-FU细胞系中过表达，这表明sCLU的上调与抗癌药的化学耐药性密切相关。在本研究中，我们旨在阐明sCLU在调节胃癌细胞化学耐药性中的作用和机制。通过膜联蛋白V /碘化丙啶染色和CCK8评估细胞凋亡和细胞活力。使用定量RT-PCR测定法检测sCLU和miR-195-5P的表达。通过RT-PCR检测sCLU在胃癌组织中的表达。通过上调或下调胃癌细胞中的sCLU或miR-195-5P来评估化学耐药的机制。我们发现sCLU在MGC-803 / 5-FU和SGC-7901细胞中显着升高，而下调sCLU则通过上调miR-195-来使MGC-803 / 5-FU和SGC-7901细胞对顺铂和多西他赛敏感。 5P。通过下调miR-195-5p，在MGC-803和HGC-27细胞中上调sCLU对顺铂和多西他赛具有抗性。靶向miR-195-5P降低了MGC-803细胞对5-FU的敏感性，而miR-195-5P过表达提高了MGC-803 / 5-FU细胞对5-FU的敏感性。sCLU在胃癌组织中的过表达与化学抗性有关。我们的发现表明，sCLU的过表达通过下调miR-195-5p诱导胃癌细胞的化学耐药性，