Zhou Peng, Zheng Zi-Han, Wan Tao, Wu Jie, Liao Chuan-Wen, Sun Xue-Jun
Department of General Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Department of Gastrointestinal Surgery, Jiangxi Provincial People's Hospital, Nanchang, People's Republic of China.
J Gastric Cancer. 2021 Dec;21(4):439-456. doi: 10.5230/jgc.2021.21.e40. Epub 2021 Dec 31.
Gastric cancer (GC) has high morbidity and mortality and is a serious threat to public health. The flavonoid compound vitexin is known to exhibit anti-tumor activity. In this study, we explored the therapeutic potential of vitexin in GC and its underlying mechanism.
The viability, migration, and invasion of GC cells were determined using MTT, scratch wound healing, and transwell assays, respectively. Target molecule expression was determined by western blotting. Tumor growth and liver metastasis were evaluated in vivo using nude mice. Protein expression in the tumor tissues was examined by immunohistochemistry.
Vitexin inhibited GC cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT) in a dose-dependent manner. Vitexin treatment led to the inactivation of phosphatidylinositol-3-kinase (PI3K)/AKT/hypoxia-inducible factor-1α (HIF-1α) pathway by repressing expression. Vitexin-mediated inhibition in proliferation, migration, invasion and EMT of GC cells were counteracted by hyper-activation of PI3K/AKT/HIF-1α pathway or overexpression. Finally, vitexin inhibited the xenograft tumor growth and liver metastasis in vivo by suppressing HMGB1 expression.
Vitexin inhibited the malignant progression of GC in vitro and in vivo by suppressing HMGB1-mediated activation of PI3K/Akt/HIF-1α signaling pathway. Thus, vitexin may serve as a promising therapeutic agent for the treatment of GC.
胃癌（GC）发病率和死亡率高，严重威胁公众健康。已知黄酮类化合物牡荆素具有抗肿瘤活性。在本研究中，我们探讨了牡荆素在胃癌中的治疗潜力及其潜在机制。
分别采用MTT法、划痕伤口愈合实验和Transwell实验测定胃癌细胞的活力、迁移和侵袭能力。通过蛋白质印迹法测定靶分子的表达。使用裸鼠在体内评估肿瘤生长和肝转移情况。通过免疫组织化学检测肿瘤组织中的蛋白质表达。
牡荆素以剂量依赖性方式抑制胃癌细胞的活力、迁移、侵袭和上皮-间质转化（EMT）。牡荆素处理通过抑制表达导致磷脂酰肌醇-3-激酶（PI3K）/AKT/缺氧诱导因子-1α（HIF-1α）信号通路失活。PI3K/AKT/HIF-1α信号通路的过度激活或的过表达可抵消牡荆素介导的对胃癌细胞增殖、迁移、侵袭和EMT的抑制作用。最后，牡荆素通过抑制HMGB1表达在体内抑制异种移植肿瘤的生长和肝转移。
牡荆素通过抑制HMGB1介导的PI3K/Akt/HIF-1α信号通路激活，在体外和体内抑制胃癌的恶性进展。因此，牡荆素可能是一种有前途的胃癌治疗药物。
