College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China.
School of Medicine and Pharmacy, Ocean University of China, QingDao, China.
Nutr Cancer. 2022;74(5):1780-1791. doi: 10.1080/01635581.2021.1960385. Epub 2021 Oct 3.
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 protein (pPep) in gastric cancer. Microarray analysis was performed to find out differentially expressed genes in pPep-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 pPep-treated gastric cancer cell lines with IL-6 or NSC74859. The anti-tumor effect was increased when pPep 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. pPep 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 pPep, 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.
胃癌是全球癌症相关死亡的主要原因。本研究旨在探讨纯化蛋白（pPep）对胃癌的抗肿瘤作用。通过微阵列分析发现 pPep 处理的 MC-4 胃癌细胞中差异表达的基因。基于生物信息学分析，最有可能改变 Janus 激酶（JAK）/信号转导和转录激活因子（STAT）三信号通路。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。用 IL-6 或 NSC74859 处理 pPep 处理的胃癌细胞系，通过流式细胞术和 MTS 分析进行细胞增殖和活力分析。当 pPep 与 IL-6 共同处理时，抗肿瘤作用增加，而在抑制剂处理时则减少。通过 Western blot 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、细胞因子信号转导抑制剂 SOCS1 和 SOCS3。pPep 在 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 抑制部分有助于 pPep 的抗癌作用，这可能成为胃癌的一种新策略。本文的补充数据可在 https://doi.org/10.1080/01635581.2021.1960385 在线获取。
