TRPV3 promotes the angiogenesis through HIF-1α-VEGF signaling pathway in A549 cells

作者：Li, Xiaolei; Li, Huifeng; Li, Zhonghua; Wang, Tingting; Yu, Dejun; Jin, Hongbo^*; Cao, Yonggang^*

来源：Acta Histochemica, 2022, 124(8): 151955.

DOI：10.1016/j.acthis.2022.151955

• TRPV3
• HIF-1?
• VEGF
• Non-small cell lung cancer
• Angiogenesis?

Background: Angiogenesis is an essential physiological process in the growth and metastasis of primary tumors. Ca2+ signaling is crucial for tumor angiogenesis. The purpose of this study was to detect the potential role of Ca2+ permeable transient receptor potential vanilloid-3 (TRPV3) in the angiogenesis of non-small cell lung cancer (NSCLC). Methods: Small interfering RNA was used to down-regulate TRPV3 expression in A549 cells. A laser scanning confocal microscope was used to examine intracellular calcium concentration ([Ca2+]i). Human umbilical vein endothelial cells (HUVECs) tube formation and migration assay, Western blot, MTT and ELISA were performed to detect the potential mechanisms of TRPV3 in tumor angiogenesis. A mouse tumor xenograft model was per -formed to expound the effects of TRPV3 on tumor cell growth. Results: Inhibition of TRPV3 reduced [Ca2+]i and protein expressions of VEGF and HIF-1 alpha in A549 cells. Moreover, HIF-1 alpha depletion decreased the secretion and expression of VEGF. Depletion of TRPV3 inhibited HUVECs proliferation, tube formation and migration induced by conditioned medium. And TRPV3 inhibition could decrease the volume of xenograft tumors and MVD of CD34+ cells. The expression levels of HIF-1 alpha, VEGF and p-CaMKn in the xenograft tumors in RuR and siTRPV3 groups was reduced. Conclusions: TRPV3 calcium channel protein may play a key role in NSCLC angiogenesis. TRPV3 could promote the angiogenesis through HIF-1 alpha-VEGF signaling pathway. Targeting TRPV3 channel protein by novel ap-proaches would be useful for reversing NSCLC angiogenesis.

• 单位
  哈尔滨医科大学