Effect of HIF-1αon malignancy of human glioma SHG44 cells and its possible mechanism
CHEN Jian1, GUO Zhijuan2, PEI Meijuan3, FU Lihua4, HUANG Shengxuan5
1. Department of Nerve Trauma Repair, 3. Department of Neurology, 4. Military General Medicine Department, Characteristic Medical Center of Chinese People’s Armed Police Force, Tianjin 300162, China; 2. The Third Medical Genter of Chinese PLA General Hospital, Beijing 100039, China; 5. Department of Neurosurgery,Sanming First Hospital Affiliated to Fujian Medical University,Sanming 365000,China
Abstract:Objective To investigate the effect of hypoxia inducible factor-1 α (HIF-1α) overexpression on the malignancy of human glioma SHG44 cells and its possible mechanism.Methods Glioma cell SHG44 was cultured in vitro and transfected with HIF-1α overexpression into SHG44 cells. The effects of HIF-1α overexpression on the growth and proliferation, cell stem, invasion and metastasis of tumor cells in vitro were analyzed. Finally, the relationship between HIF-1α and pyroptosis were clarified by detecting the expression of HIF-1α, tumor-associated inflammatory factors(TNF- α, IL-10, IL-17 and IL-1 β), pyroptosis markers [inflammatory body 3 (NLRP3), apoptosis associated speck like protein (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), GSDMD, GSDME and transforming growth factor-β1(TGF-β1nd).Results MTT, cell cloning, cell scratch and Transwell experiments confirmed that the morphological swelling of SHG44 cells increased significantly after the overexpression of HIF-1α, and cell proliferation and invasion ability were significantly enhanced compared with the control group; ELISA showed that, compared with the control group, tumor inflammatory factor (TNF α,IL-10 and IL-1 β)increased significantly, while IL-17 decreased significantly; RT-PCR and Western blot showed that the expression level of HIF-1α in glioma cell line was higher than that in normal brain cells The expression levels of NLRP3, ASC, caspase-1, GSDMD and GSDME inHIF-1αoverexpression group were significantly higher than those in control group (P<0.05).Conclusions The increased expression of HIF-1α in glioma cells SHG44 can increase the proliferation and invasion of glioma cells, which may be achieved by promoting pyroptosis.
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