|
|
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.
|
Received: 10 January 2022
|
|
|
|
|
[1] |
陈圣攀,左晓坤,夏 鹰. 脑胶质瘤的治疗进展[J]. 中华神经创伤外科电子杂志, 2017, 3(2):105-107.
|
[2] |
Xi X, Liu N, Wang Q, et al. ACT001, a novel PAI-1 inhibitor, exerts synergistic effects in combination with cisplatin by inhibiting PI3K/AKT pathway in glioma[J]. Cell Death Dis, 2019,10(10):757.
|
[3] |
Bent M J, Chang S M.Grade II and III oligodendroglioma and astrocytoma[J]. Neurol Clin,2018,36(3):467-484.
|
[4] |
Semenza G L.Pharmacologic targeting of hypoxia-inducible factors[J]. Annu Rev Pharmacol Toxicol, 2019,59:379-403.
|
[5] |
Liu N, Luo J, Kuang D,et al. Lactate inhibits ATP6V0d2 expression in tumor-associated macrophages to promote HIF-2α-mediated tumor progression[J]. J Clin Invest, 2019,129(2):631-646.
|
[6] |
Bao L, Chen Y, Lai HT,et al. Methylation of hypoxia-inducible factor (HIF)-1α by G9a/GLP inhibits HIF-1 transcriptional activity and cell migration[J]. Nucleic Acids Res,2018,46(13):6576-6591.
|
[7] |
覃高升,李佳乐,王婉婉,等. 细胞焦亡在肿瘤中的研究进展[J]. 癌症进展, 2020,12(4):339-342.
|
[8] |
Gulluoglu S, Tuysuz E C, Sahin M,et al. Simultaneous miRNA and mRNA transcriptome profiling of glioblastoma samples reveals a novel set of OncomiR candidates and their target genes[J]. Brain Res, 2018,1700:199-210.
|
[9] |
袁琳琳, 喻晓芬. miR-202通过降低肝癌细胞ROCK1表达抑制其迁移和侵袭[J]. 温州医科大学学报, 2019,49(3):204-209.
|
[10] |
Li L C, Zhang M, Feng Y K, et al. IDH1-R132H suppresses glioblastoma malignancy through FAT1-ROS-HIF-1α signaling[J]. Neurol India, 2020,68(5):1050-1058.
|
[11] |
何亚运, 罗泊涛, 陆元志. 肿瘤微环境中免疫抑制性细胞和细胞因子在抗肿瘤免疫反应中的作用研究进展[J]. 山东医药, 2019, 59(6):88-92.
|
[12] |
Cruceriu D, Baldasici O, Balacescu O, et al. The dual role of tumor necrosis factor-alpha (TNF-α) in breast cancer: molecular insights and therapeutic approaches[J]. Cell Oncol (Dordr), 2020,43(1):1-18.
|
[13] |
Dadaglio G, Fayolle C, Oberkampf M, et al. IL-17 suppresses the therapeutic activity of cancer vaccines through the inhibition of CD8+ T-cell responses[J]. Oncoimmunology, 2020,9(1):1758606.
|
[14] |
Nishida J, Miyazono K, Ehata S.Decreased TGFBR3/betaglycan expression enhances the metastatic abilities of renal cell carcinoma cells through TGF-β-dependent and -independent mechanisms[J]. Oncogene,2018,37(16):2197-2212.
|
[15] |
景艳芸,李陈广,颜 亮, 等. 灯盏花乙素对J774A.1巨噬细胞中ATP诱导的炎性反应小体活化和细胞焦亡的影响[J]. 中国药理学通报, 2018,34(2):174-180.
|
[16] |
Dhanasekaran D N, Reddy E P. JNK-signaling: A multiplexing hub in programmed cell death[J]. Genes Cancer, 2017,8(9-10):682-694.
|
[17] |
Wang Y, Yin B, Li D, et al. GSDME mediates caspase-3-dependent pyroptosis in gastric cancer[J]. Biochem Biophys Res Commun, 2018,495(1):1418-1425.
|
[18] |
朱 光, 陈丽艳, 林贞花. 细胞焦亡与肿瘤治疗研究进展[J]. 临床与实验病理学杂志, 2018, 34(10):1126-1130.
|
[19] |
Zhu S, Zhang Z, Jia L Q, et al. Valproic acid attenuates global cerebral ischemia/reperfusion injury in gerbils via anti-pyroptosis pathways[J]. Neurochem Int, 2019,124:141-151.
|
[20] |
Kelley N, Jeltema D, Duan Y, et al. The NLRP3 Inflammasome: an overview of mechanisms of activation and regulation[J]. Int J Mol Sci, 2019,20(13):3328.
|
[21] |
Zhang D, Qian J, Zhang P,et al. Gasdermin D serves as a key executioner of pyroptosis in experimental cerebral ischemia and reperfusion model both in vivo and in vitro[J]. J Neurosci Res, 2019,97(6):645-660.
|
|
|
|