PlGF knockdown attenuates hypoxia-induced stimulation of cell proliferation and glycolysis of lung adenocarcinoma through inhibiting Wnt/β-catenin pathway.
PlGF knockdown attenuates hypoxia-induced stimulation of cell proliferation and glycolysis of lung adenocarcinoma through inhibiting Wnt/β-catenin pathway.
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PlGF 敲低通过抑制 Wnt/β-连环蛋白途径减弱缺氧诱导的细胞增殖刺激和肺腺癌糖酵解。
DOI：
10.1186/s12935-020-01714-w
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发表时间：
2021-01-06
影响因子：
5.8
通讯作者：
Han B
中科院分区：
文献类型：
--
作者：
Zhang W;Zhang Y;Zhou W;Qian F;Hu M;Chen Y;Lu J;Lou Y;Han B
胎盘生长因子（PlGF）在缺氧诱导的血管生成中起作用。本研究旨在探讨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。用慢病毒在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 h。在Wnt/β-catenin信号通路抑制剂XAV939处理的PC9细胞中，PlGF过表达。将plgf沉默的H1975细胞植入小鼠体内，收获肿瘤异种移植物并进行分析。缺氧处理导致H358和H1975细胞PlGF、C-myc、乳酸脱氢酶A （LDHA）和β-catenin表达上调，促进细胞增殖和糖酵解，而下调PlGF可明显逆转这一过程。在肿瘤中，PlGF敲低显著抑制细胞增殖和糖酵解，降低C-myc、LDHA和β-catenin的表达。PlGF过表达可显著增强细胞增殖，而下调β-catenin可抑制细胞增殖。同样，Wnt/β-catenin通路抑制剂XAV939也抑制plgf诱导的PC9细胞增殖、糖酵解和β-catenin的表达。PlGF敲低通过使Wnt/β-catenin通路失活，抑制缺氧对LUAD细胞增殖和糖酵解的刺激作用。
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. PlGF was knocked down in H358 and H1975 cells by lentiviruses, which were then cultured under hypoxia (90% N2, 5%CO2 and 5%O2) 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. 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. PlGF knockdown inhibited the stimulatory effect of hypoxia on cell proliferation and glycolysis of LUAD through deactivating Wnt/β-catenin pathway.
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影响因子：
5.4
作者：
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通讯作者：
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影响因子：
30.8
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2.8
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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