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槲皮素与奥沙利铂联合诱导 SGC-7901 胃癌细胞凋亡中 P38 信号转导通路的更多协同因子。

P38 Signal Transduction Pathway Has More Cofactors on Apoptosis of SGC-7901 Gastric Cancer Cells Induced by Combination of Rutin and Oxaliplatin.

机构信息

Department of Pathology, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China.

Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin, China.

出版信息

Biomed Res Int. 2019 Nov 6;2019:6407210. doi: 10.1155/2019/6407210. eCollection 2019.

Abstract

Currently, gastric cancer treatment is mainly based on first-line intervention with oxaliplatin (OXA) after surgical resection, but the application of OXA has been limited due to the toxic side effects caused by the cumulative dose. The toxicity of OXA mainly includes hepatotoxicity, nephrotoxicity, and ototoxicity, and there is an urgent clinical need to find alternatives that are less toxic and more effective. Rutin (RT) is a natural flavonoid with many biological activities. Studies have found that RT inhibits tumor cell growth and enhances their sensitivity toward certain drugs. As the underlying impact of RT on gastric cancer and its molecular mechanism remain poorly understood, we performed a series of experiments to determine whether RT has the effect of treating gastric cancer, and whether it can cooperate with OXA to treat gastric cancer and its related mechanisms. In the present study, we founded that RT suppressed cell viability, inhibited cell proliferation by causing G0/G1 arrest, and induced apoptosis in SGC 7901 cells. And RT can play as an antitumor agent together with OXA. The mechanism of RT-induced apoptosis may be associated with the activation of the p38/Caspase signal pathway. These results demonstrated the potential of RT as a promising therapeutic compound to treat gastric cancer. At the same time, RT can synergize with OXA to reduce the dose of OXA and reduce the toxicity.

摘要

目前,胃癌的治疗主要基于手术切除后的一线奥沙利铂(OXA)干预,但由于累积剂量引起的毒副作用,OXA 的应用受到限制。OXA 的毒性主要包括肝毒性、肾毒性和耳毒性,临床上迫切需要寻找毒性更小、更有效的替代品。芦丁(RT)是一种具有多种生物活性的天然类黄酮。研究发现,RT 抑制肿瘤细胞生长并增强其对某些药物的敏感性。由于 RT 对胃癌的潜在影响及其分子机制仍不清楚,我们进行了一系列实验,以确定 RT 是否具有治疗胃癌的作用,以及它是否可以与 OXA 联合治疗胃癌及其相关机制。在本研究中,我们发现 RT 通过引起 G0/G1 期阻滞抑制细胞增殖,从而抑制 SGC 7901 细胞活力并诱导细胞凋亡。并且 RT 可以与 OXA 一起作为抗肿瘤药物发挥作用。RT 诱导细胞凋亡的机制可能与 p38/Caspase 信号通路的激活有关。这些结果表明 RT 具有作为治疗胃癌的有前途的治疗化合物的潜力。同时,RT 可以与 OXA 协同作用,降低 OXA 的剂量并降低毒性。

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