胎盘生长因子（PlGF）基因敲低通过抑制Wnt/β-连环蛋白信号通路，减弱缺氧诱导的肺腺癌细胞增殖和糖酵解刺激。

PlGF knockdown attenuates hypoxia-induced stimulation of cell proliferation and glycolysis of lung adenocarcinoma through inhibiting Wnt/β-catenin pathway.

作者信息

Zhang Wei, Zhang Yanwei, Zhou Wensheng, Qian Fangfei, Hu Minjuan, Chen Ya, Lu Jun, Lou Yuqing, Han Baohui

机构信息

Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, People's Republic of China.

出版信息

Cancer Cell Int. 2021 Jan 6;21(1):18. doi: 10.1186/s12935-020-01714-w.

DOI:10.1186/s12935-020-01714-w

PMID:33407494

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7788771/

Abstract

BACKGROUND

Angiogenic placental growth factor (PlGF) plays a role in hypoxia-induced angiogenesis. Here, we aimed to investigate the biological roles of PlGF in cell proliferation and glycolysis of lung adenocarcinoma (LUAD) and the underlying molecular mechanisms.

METHODS

PlGF was knocked down in H358 and H1975 cells by lentiviruses, which were then cultured under hypoxia (90% N, 5%CO and 5%O) for 24 h. PlGF was overexpressed in PC9 cells treated with XAV939, inhibitor of Wnt/β-catenin signaling pathway. PlGF-silencing H1975 cells were implanted into mice, and tumor xenografts were harvested and analyzed.

RESULTS

Hypoxia treatment led to up-regulation of PlGF, C-myc, lactate dehydrogenase A (LDHA), and β-catenin, promotion of cell proliferation and glycolysis in H358 and H1975 cells, which were obviously reversed by knocking down PlGF. In tumors, PlGF knockdown significantly prohibited cell proliferation and glycolysis, and decreased expression of C-myc, LDHA, and β-catenin. PlGF overexpression markedly strengthened cell proliferation, which was inhibited by β-catenin knockdown. Consistently, XAV939, inhibitor of Wnt/β-catenin pathway, also inhibited PlGF-induced cell proliferation, glycolysis, and β-catenin expression in PC9 cells.

CONCLUSION

PlGF knockdown inhibited the stimulatory effect of hypoxia on cell proliferation and glycolysis of LUAD through deactivating Wnt/β-catenin pathway.

摘要

背景

血管生成性胎盘生长因子（PlGF）在缺氧诱导的血管生成中起作用。在此，我们旨在研究PlGF在肺腺癌（LUAD）细胞增殖和糖酵解中的生物学作用及其潜在的分子机制。

方法

通过慢病毒在H358和H1975细胞中敲低PlGF，然后在缺氧（90%N₂、5%CO₂和5%O₂）条件下培养24小时。在用Wnt/β-连环蛋白信号通路抑制剂XAV939处理的PC9细胞中过表达PlGF。将PlGF沉默的H1975细胞植入小鼠体内，收获并分析肿瘤异种移植瘤。

结果

缺氧处理导致H358和H1975细胞中PlGF、C-myc、乳酸脱氢酶A（LDHA）和β-连环蛋白上调，促进细胞增殖和糖酵解，敲低PlGF可明显逆转这些作用。在肿瘤中，PlGF敲低显著抑制细胞增殖和糖酵解，并降低C-myc、LDHA和β-连环蛋白的表达。PlGF过表达显著增强细胞增殖，β-连环蛋白敲低可抑制该作用。同样，Wnt/β-连环蛋白通路抑制剂XAV939也抑制PC9细胞中PlGF诱导的细胞增殖、糖酵解和β-连环蛋白表达。