eEF2K knockdown synergizes STS to inhibit the angiogenesis of lung adenocarcinoma via TG2/IL-6/VEGFR2 pathway

Abstract

Background: Lung adenocarcinoma (LUAD) is the most popular type of lung cancer. Eukaryotic elongation factor 2 kinase (eEF2K) is considered to be a carcinogen, and Sulfotanshinone IIA sodium (STS) has been proved to have anticancer effect. However, their role in LUAD and its underlying mechanism remains unclear.Objective: To figuring out the roles of eEF2K and STS in angiogenesis of LUAD and their underlying mechanism.Methods: The mRNA levels of genes were detected by qRT-PCR. The levels of proteins were measured by Western blot. The secretion of IL-6 was assessed by ELISA. The proliferation and angiogenesis of human umbilical vein endothelial cells (HUVECs) were detected by EdU assay and tubule formation assay, respectively.Results: Our results illustrated that eEF2K knockdown-LUAD cells synergize STS inhibited the proliferation and angiogenesis of HUVECs, eEF2K knockdown synergized STS inhibited the secretion of interleukin 6 (IL-6) in LUAD cells, and eEF2K knockdown-LUAD cells synergized STS to inhibit the proliferation and angiogenesis of HUVECs, which were dependent on IL-6 secretion and Transglutaminase 2 (TG2). Moreover, eEF2K knockdown-LUAD cells synergized STS inhibited IL-6/STAT3/VEGFR2 pathway depended on TG2. Conclusion: Our research ultimately illustrated that eEF2K knockdown synergized STS to inhibit the angiogenesis of LUAD via TG2/IL-6/VEGFR2 pathway.