As the endogenous ligand for the GH secretagogue receptor (GHSR), Ghrelin is aberrant expressed in multiple malignant carcinoma, and involved in regulating a number of progression of cancer, especially in metastasis and proliferation. However, the precise role of Ghrelin in tumorigenesis of gastric cancer (GC) is still poorly understood. In this study, we extensively investigated the roles and mechanisms of Ghrelin in human gastric cancer. Ghrelin levels in cancer tissues and cell lines were analyzed by immunohistochemistry, qRT-PCR, and Western blot. Functional studies were performed after Ghrelin overexpressed or knockdown in AGS cell line. Cell proliferation was evaluated in by MTT and clone formation assays. The wound healing and Transwell system were used to assess the cell migration and invasive ability of GC cells. Cell apoptosis was detected by flow cytometry, and metabolic assays were performed to reveal the function of Warburg effect in the process. Ghrelin was lowly expressed in gastric cancer tissues and cell lines. Overexpression of Ghrelin inhibited gastric cancer cell proliferation, migration, invasion, and promoted apoptosis by activating the AMPK pathway, while d-[lys3]-GHRP-6 (a GHSR agonist) treatment relieved the effect, promoting tumorigenesis. Ghrelin knockdown increased the glucose uptake and lactic acid release, suggesting that Ghrelin elicited an anti-Warburg effect via AMPK pathway to inhibit gastric tumorigenesis. Ghrelin inhibits cell proliferation, migration, and invasion by eliciting an anti-Warburg effect via AMPK signaling pathway in gastric cancer cells.

作为GH促分泌素受体(GHSR)的内源性配体，Ghrelin在多发性恶性肿瘤中异常表达，参与调控多种癌症的进展，尤其是转移和增殖。然而，Ghrelin 在胃癌 (GC) 肿瘤发生中的确切作用仍知之甚少。在这项研究中，我们广泛研究了 Ghrelin 在人类胃癌中的作用和机制。通过免疫组织化学、qRT-PCR 和蛋白质印迹分析癌组织和细胞系中的生长素释放肽水平。在 Ghrelin 在 AGS 细胞系中过表达或敲低后进行功能研究。通过MTT和克隆形成测定评估细胞增殖。伤口愈合和Transwell系统用于评估GC细胞的细胞迁移和侵袭能力。通过流式细胞术检测细胞凋亡，并进行代谢测定以揭示Warburg效应在该过程中的作用。Ghrelin在胃癌组织和细胞系中低表达。Ghrelin过表达通过激活AMPK通路抑制胃癌细胞增殖、迁移、侵袭、促进细胞凋亡，而d -[lys3]-GHRP-6（一种 GHSR 激动剂）治疗可缓解该效应，促进肿瘤发生。Ghrelin 敲低增加了葡萄糖摄取和乳酸释放，表明 Ghrelin 通过 AMPK 通路引发抗 Warburg 效应以抑制胃肿瘤发生。Ghrelin 通过 AMPK 信号通路在胃癌细胞中引发抗 Warburg 效应，从而抑制细胞增殖、迁移和侵袭。