Abstract

Hypoxia is a frequent occurrence in most solid tumors and associated with multiple cancer progression. Glaucocalyxin A (GLA) has been found to exhibit anti-tumor effect in several types of cancer, except gastric cancer (GC). The present study aimed to evaluate the function of GLA in GC and explore the underlying mechanism under hypoxia condition. Our results showed that GLA suppressed cell viability of MGC-803 cells in both normoxic or hypoxic conditions. MGC-803 cells were more sensitive to GLA in hypoxic condition. GLA attenuated hypoxia-induced migration and invasion of GC cells. Western blot assay proved that GLA elevated E-cadherin expression, as well reduced N-cadherin and vimentin expressions in hypoxia-induced GC cells. Moreover, we also found that GLA suppressed the expression of HIF-1α in both mRNA and protein levels. Furthermore, GLA blocked hypoxia-induced activation of PI3K/Akt pathway in GC cells. Notably, insulin like growth factor 1 (IGF-1), an activator of PI3K/Akt pathway, reversed the effects of GLA on cell migration, invasion and EMT in hypoxia-treated MGC-803 cells. In conclusion, these findings demonstrated that GLA exerted inhibitory effects on cell migration, invasion and epithelial to mesenchymal transition (EMT) via the PI3K/Akt signaling pathway in GC cells.

摘要

缺氧在大多数实体瘤中很常见，并且与多种癌症进展有关。已发现 Glaucocalyxin A (GLA) 在几种类型的癌症中表现出抗肿瘤作用，除了胃癌 (GC)。本研究旨在评估 GLA 在 GC 中的功能，并探讨低氧条件下的潜在机制。我们的结果表明，在常氧或缺氧条件下，GLA 抑制 MGC-803 细胞的细胞活力。MGC-803细胞在缺氧条件下对GLA更敏感。GLA减弱了低氧诱导的GC细胞迁移和侵袭。蛋白质印迹分析证明，GLA 可提高缺氧诱导的 GC 细胞中 E-cadherin 的表达，同时降低 N-cadherin 和 vimentin 的表达。此外，我们还发现 GLA 在 mRNA 和蛋白质水平上均抑制 HIF-1α 的表达。此外，GLA 阻断低氧诱导的 GC 细胞中 PI3K/Akt 通路的激活。值得注意的是，胰岛素样生长因子 1 (IGF-1) 是 PI3K/Akt 通路的激活剂，可逆转 GLA 对缺氧处理的 MGC-803 细胞中细胞迁移、侵袭和 EMT 的影响。总之，这些发现表明 GLA 对细胞迁移、侵袭和上皮间质转化 (EMT) 具有抑制作用通过GC 细胞中的 PI3K/Akt 信号通路。