Anti-Gastric Cancer Effect of Purified Omphalia lapidescens Protein via Regulating the JAK/STAT3 Signaling Pathway
Anti-Gastric Cancer Effect of Purified Omphalia lapidescens Protein via Regulating the JAK/STAT3 Signaling Pathway
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纯化的 Omphalia lapidescens 蛋白通过调节 JAK/STAT3 信号通路的抗胃癌作用
DOI：
10.1080/01635581.2021.1960385
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Yitao Chen
中科院分区：
文献类型：
--
作者：
Yuqin Xu;Wenjun Xu;Zhongxia Lu;Man Hei Cheung;Meiai Lin;Chun Liang;Jianshu Lou;Yitao Chen
摘要 胃癌是全球癌症相关死亡的主要原因。本研究的目的是探讨纯化的 Omphalia lapidescens 蛋白 (pPeOp) 在胃癌中的抗肿瘤作用。进行微阵列分析以找出 pPeOp 处理的 MC-4 胃癌细胞中差异表达的基因。根据生物信息学分析，Janus 激酶（JAK）/信号转导子和转录激活子（STAT）三个信号通路最有可能被改变。白细胞介素-6 (IL-6) 和 NSC74859 分别用作 JAK/STAT3 信号通路的激动剂和抑制剂。使用流式细胞术和 MTS 测定法对经 IL-6 或 NSC74859 处理的 pPeOp 胃癌细胞系进行细胞增殖和活力分析。当pPeOp与IL-6共同处理时，抗肿瘤作用增强，而抑制剂处理时抗肿瘤作用减弱。通过蛋白质印迹法检测MC-4细胞通路中关键成员的表达，包括糖蛋白130（GP130）、JAK1、JAK2、STAT3、p-STAT3、细胞因子信号传导抑制因子SOCS1和SOCS3。 pPeOp 在通过 STAT3 敲低胃癌细胞建立的异种移植裸鼠模型中表现出良好的抗癌作用。因此，JAK/STAT3 抑制部分促进了 pPeOp 的抗癌作用，这可能作为胃癌的一种新策略。本文的补充数据可在线获取：https://doi.org/10.1080/01635581.2021.1960385
Abstract Gastric cancer is the leading cause of cancer-related death worldwide. The aim of present study was to investigate the anti-tumor effect of purified Omphalia lapidescens protein (pPeOp) in gastric cancer. Microarray analysis was performed to find out differentially expressed genes in pPeOp-treated MC-4 gastric cancer cells. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) three signaling pathway was most likely to be altered based on bioinformatics analysis. Interleukin-6 (IL-6) and NSC74859 were used as the agonist and inhibitor of the JAK/STAT3 signaling pathway, respectively. Flow cytometry and MTS assay were used for cell proliferation and viability analysis in pPeOp-treated gastric cancer cell lines with IL-6 or NSC74859. The anti-tumor effect was increased when pPeOp were co-treated with IL-6, while decreased in inhibitor treatment. The expression of the crucial members in the pathway of MC-4 cells, including glycoprotein 130 (GP130), JAK1, JAK2, STAT3, p-STAT3, suppressor of cytokine signaling SOCS1 and SOCS3, was detected by western blotting. pPeOp exhibited promising anticancer effect in the xenograft nude mice model, established by STAT3 knock down gastric cancer cells.Thus, JAK/STAT3 inhibition partially contributed to the anticancer effect of pPeOp, which may serve as a novel strategy for gastric cancer. Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1960385
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