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Targeting valosin‐containing protein enhances the efficacy of radiation therapy in esophageal squamous cell carcinoma

机译:靶向含valosin的蛋白可增强食道鳞状细胞癌的放射治疗功效

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摘要

Overcoming resistance to radiation is a great challenge in cancer therapy. Here, we highlight that targeting valosin‐containing protein ( ) improves radiation sensitivity in esophageal squamous cell carcinoma ( ) cell lines and show the potential of using as a prognosis marker in locally advanced treated with radiation therapy. Esophageal squamous cell carcinoma cell lines with high expression were treated with inhibitor combined with radiotherapy. Cell proliferation, colony formation, cell death, and endoplasmic reticulum ( ) stress signaling were evaluated. Moreover, patients with newly diagnosed locally advanced who were treated with radiotherapy were analyzed. Immunohistochemistry was used to detect the expression of . The correlation between overall survival and was investigated. Esophageal squamous cell carcinoma cells treated with inhibitor and radiotherapy showed attenuated cell proliferation and colony formation and enhanced apoptosis. Further investigation showed this combined strategy activated the stress signaling involved in unfolded protein response, and inhibited the ‐associated degradation ( ) pathway. Clinical analysis revealed a significant survival benefit in the low expression group. Targeting resulted in antitumor activity and enhanced the efficacy of radiation therapy in cells in vitro. Valosin‐containing protein is a promising and novel target. In patients with locally advanced who received radiotherapy, can be considered as a useful prognostic indicator of overall survival. Valosin‐containing protein inhibitors could be developed for use as effective cancer therapies, in combination with radiation therapy.
机译:克服对放射线的抵抗力是癌症治疗中的巨大挑战。在这里,我们强调了靶向含缬氨酸的蛋白质()可提高食道鳞状细胞癌()细胞系的放射敏感性,并显示出在局部晚期放射治疗中用作预后标志物的潜力。用抑制剂联合放疗治疗高表达的食管鳞癌细胞株。评价了细胞增殖,集落形成,细胞死亡和内质网应激信号。此外,对接受放射治疗的新诊断为局部晚期的患者进行了分析。免疫组织化学法检测鼻咽癌的表达。与总生存期之间的相关性进行了研究。食管鳞状细胞癌细胞经抑制剂和放射治疗后,细胞增殖和集落形成减弱,凋亡增加。进一步的研究表明,这种联合策略激活了涉及未折叠蛋白质反应的应激信号传导,并抑制了相关的降解()途径。临床分析显示,低表达组具有明显的生存获益。靶向导致抗肿瘤活性并增强体外细胞放射治疗的功效。含Valosin的蛋白质是一个有前途的新目标。在接受放疗的局部晚期患者中,可以将其视为总体生存的有用预后指标。含缬沙星的蛋白抑制剂可与放射疗法结合起来用作有效的癌症疗法。

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