EPO/EPOR信号通路对胃癌的肿瘤促进作用
EPO/EPOR信号通路对胃癌的肿瘤促进作用
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作者：
Weiling Hu;Yu Zhang;Zhinong Jiang;LanWang;Jun Li;Shujie Chen;Ning Dai;Jianmin Si
促红细胞生成素（EPO）与其受体（EPOR）结合，在红细胞生成中起重要作用。据报道，EPOR在包括胃癌在内的多种非造血肿瘤中表达。虽然重组人促红细胞生成素（rhEPO）在临床上已广泛应用于贫血患者，但其是否会促进肿瘤进展仍存在争议。本研究采用siRNA干扰法下调EPOR表达，探讨EPO/EPOR通路在人胃癌细胞中的功能。我们发现EPOR在胃癌组织和大多数胃癌细胞系中表达显著升高。RhEPO促进胃癌细胞在AGS细胞中的增殖和迁移，促进细胞从G0/G1期向G2/M期转移，但对AGS细胞凋亡无调节作用。通过siRNA干扰下调EPOR的表达。对AGS细胞的增殖和侵袭性无显著影响，但可诱导细胞凋亡（p<0.05）。采用异种移植胃肿瘤模型，探讨其对胃肿瘤的影响。epor过表达对体内胃癌细胞的影响。结果表明，过表达EPOR促进裸鼠肿瘤形成（p< 0.01）。我们的研究结果表明，EPO/EPOR通路促进胃癌的形成、增殖、迁移，并减少凋亡。
Erythropoietin (EPO), binding with its receptor (EPOR), plays an important role in erythropoiesis. EPOR is reported to be expressed in various non-hematopoietic cancers, including gastric cancer. Although recombinant human EPO (rhEPO) has been widely used clinically in anemia patients, it remains controversial whether it would promote tumor progression. In this study, we used siRNA interference method to downregulate EPOR expression to investigate the function of EPO/EPOR pathway in human gastric cancer cells. We found EPOR expressed significantly higher in gastric cancer tissues, and also in most gastric cancer cell lines. RhEPO promoted gastric cancer cell proliferation, migration in AGS cells, and promoted cells from G0/G1 stage to G2/M stage, but had no regulation on AGS cell apoptosis. Downregulation of EPOR expression by siRNA interference.in AGS cells resulted in no significant effects on proliferation and invasiveness of the cells, but induced apoptosis (p<0.05)..Xenografted gastric tumor model was used to explore the.effect of EPOR-overexpression on gastric cancer cells in vivo. Our result showed that overexpression of EPOR enhanced tumor formation in nude mice (p< 0.01). Our results suggestthat EPO/EPOR pathway promotes gastric cancer formation, proliferation, migration, and decreases apoptosis.