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目的 东亚钳蝎氯离子通道毒素（Bmk CT）基因与非病毒载体阳离子聚合物聚乙烯亚胺（PEI）结合转染C6胶质瘤细胞，观察其对C6细胞中VEGF、MMP-9、AQP-1、p-ERK、p-AKT、p-NF-κBp65表达的影响。方法 通过生物信息学分析VEGF、MMP-9、AQP-1与胶质瘤恶性进展的关系。将PEI与空质粒pEGFP-N1和基因质粒pEGFP-N1-Bmk CT分别混合。将C6细胞分别转染PEI/pEGFP-N1和PEI/pEGFP-N1-BMKCT两种复合体。24 h后使用荧光显微镜观察转染情况。48 h后，用Western-blot检测VEGF、MMP-9、AQP-1、p-ERK、p-AKT、p-NF-κBp65蛋白表达水平。结果VEGF、MMP-9、AQP-1与胶质瘤恶性进展密切相关。24 h后观察转染成功。与PEI/pEGFP-N1组相比，PEI/pEGFP-N1-Bmk CT组在转染48 h后VEGF、MMP-9、AQP-1、p-ERK、p-AKT、p-NF-κBp65蛋白表达水平下降。结论 使用PEI/pEGFP-N1-Bmk CT复合物转染C6细胞能抑制VEGF、MMP-9、AQP-1表达，减轻肿瘤相关性水肿，这可能与ERK、AKT/NF-κB通路受抑制有关。
Abstract：Objective To investigate the effects of polyethyleneimine(PEI)-mediated Buthus martensii Karsch Chlorotoxin-like Toxin(Bmk CT), and Bmk CT gene transfection on the expression levels of VEGF, MMP-9, AQP-1, p-ERK, p-AKT and p-NF-κBp65 of C6glioma cells. Methods pEGFP-N1 and pEGFP-N1-BmK CT were respectively combined with PEI to form two complexes which were used to transfect C6 cells. After 48 hours' test by Western bloting, VEGF, MMP-9, AQP-1, p-ERK, p-AKT and p-NF-κBp65 were detected.Results The expression levels of VEGF, MMP-9, AQP-1, p-ERK, p-AKT and p-NF-κBp65 in the pEGFP-N1-Bmk CT group were significantly lower than those of the pEGFP-N1 group after the transfection. Conclusions PEI/pEGFP-N1-Bmk CT may suppress tumor associated edema through inhibiting the expressions of VEGF, MMP-9, AQP-1, p-ERK, p-AKT and p-NF-κBp65.
1 WANG LM, ENGLANDER ZK, MILLER ML, et al. Malignant glioma[J]. Adv Exp Med Biol, 2023, 1405:1-30.
2 LIU X, ZHANG X, FAN Y, et al. Effect of intraoperative goal-directed fluid therapy on the postoperative brain edema in patients undergoing high-grade glioma resections:a study protocol of randomized control trial[J]. Trials, 2022, 23(1):950.
3 ZHANG X, GUO M, SHEN L, et al. Combination of photodynamic therapy and temozolomide on glioma in a rat C6 glioma model[J]. Photodiagnosis Photodyn Ther, 2014, 11(4):603-612.
4 PREVARSKAYA N, SKRYMA R, BIDAUX G, et al. Ion channels in death and differentiation of prostate cancer cells[J]. Cell Death Differ,2007, 14(7):1295-1304.
5 DU J, FU Y, WANG J, et al. Adenovirus-mediated expression of BmK CT suppresses growth and invasion of rat C6 glioma cells[J]. Biotechnol Lett, 2013, 35(6):861-870.
6 FU Y, JIAO Y, ZHENG S, et al. Combination of lithium chloride and pEGFP-N1-BmK CT effectively decreases proliferation and migration of C6 glioma cells[J]. Cytotechnology, 2016, 68(2):197-202.
7 张亚涛,范丽娜,温春丽,等.聚乙烯亚胺介导Bmk CT基因抑制C6胶质瘤细胞C-Myc、VEGF表达[J].山西职工医学院学报, 2016(1):7-10.
8 LI W, LI Y, ZHAO Y, et al. Inhibition effects of scorpion venom extracts(Buthus matensii Karsch)on the growth of human breast cancer MCF-7cells[J]. Afr J Tradit Complement Altern Med, 2014, 11(5):105-110.
9 LE GJY, OUADID-AHIDOUCH H, SORIANI O, et al. Voltage-gated ion channels, new targets in anti-cancer research[J]. Recent Pat Anticancer Drug Discov, 2007, 2(3):189-202.
10 ROGERS ML, RUSH RA. Non-viral gene therapy for neurological diseases, with an emphasis on targeted genedelivery[J]. J Control Release,2012, 157(2):183-189.
11 ARENA TA, HARMS PD, WONG AW. High throughput transfection of HEK293 cells for transient protein production[J]. Methods Mol Biol,2018, 1850:179-187.
12 FRATI A, ARMOCIDA D, ARCIDIACONO UA, et al. Peritumoral brain edema in relation to tumor size is a variable that influences the risk of recurrence in intracranial meningiomas[J]. Tomography, 2022, 8(4):1987-1996.
13 FUJII Y, OGIWARA T, KATO H, et al. Cerebral edema due to chemotherapeutic wafer implantation for malignant glioma:registry study of correlation with perioperative epileptic seizures[J]. Neurol Med Chir(Tokyo), 2022, 62(7):328-335.
14 LI Q, QIAO G, MA J, et al. Downregulation of VEGF expression attenuates malignant biological behavior of C6 glioma stem cells[J]. Int J Oncol, 2014, 44(5):1581-1588.
15 BAKER GJ, YADAV VN, MOTSCH S, et al. Mechanisms of glioma formation:iterative perivascular glioma growth and invasion leads to tumor progression, VEGF-independent vascularization, and resistance to antiangiogenic therapy[J]. Neoplasia, 2014, 16(7):543-561.
16 BIAN XW, DU LL, SHI JQ, et al. Correlation of bFGF, FGFR-1 and VEGF expression with vascularity and malignancy of human astrocytomas[J]. Anal Quant Cytol Histol, 2000, 22(3):267-274.
17 HEISS JD, PAPAVASSILIOU E, MERRILL MJ, et al. Mechanism of dexamethasone suppression of brain tumor-associated vascular permeability in rats. Involvement of the glucocorticoid receptor and vascular permeability factor[J]. J Clin Invest, 1996, 98(6):1400-1408.
18 XU YB, DU QH, ZHANG MY, et al. Propofol suppresses proliferation,invasion and angiogenesis by down-regulating ERK-VEGF/MMP-9 signaling in Eca-109 esophageal squamous cell carcinoma cells[J]. Eur Rev Med Pharmacol Sci, 2013, 17(18):2486-2494.
19 LIANG Y, LI S. β-elemene suppresses migration of esophageal squamous cell carcinoma by modulating expression of MMP9 through the PI3K/Akt/NF-κB pathway[J]. Comb Chem High Throughput Screen,2023, 26(13):2304-2320.
20 KOMATSU K, NAKANISHI Y, NEMOTO N, et al. Expression and quantitative analysis of matrix metalloproteinase-2 and-9 in human gliomas[J]. Brain Tumor Pathol, 2004, 21(3):105-112.
21 MISHRA A, OJHA BK, CHANDRA A, et al. Choroid plexupapilloma of posterior third ventricle:A case report and review of literature[J].Asian J Neurosurg, 2014, 9(4):238.
22 OSHIO K, BINDER DK, LIANG Y, et al. Expression of the aquaporin-1water channel in human glial tumors[J]. Neurosurgery, 2005, 56(2):375-381.
23 MONZANI E, BAZZOTTI R, PEREGO C, et al. AQP1 is not only a water channel:it contributes to cell migration through Lin7/beta-catenin[J]. PLoS One, 2009, 4(7):e6167.
24 CLéMENT T, RODRIGUEZ-GRANDE B, BADAUT J. Aquaporins in brain edema[J]. J Neurosci Res, 2020, 98(1):9-18.
25 HAYASHI Y, EDWARDS NA, PROESCHOLDT MA, et al. Regulation and function of aquaporin-1 in glioma cells[J]. Neoplasia, 2007, 9(9):777-787.
26 XU J, XIE R, LIU X, et al. Expression and functional role of vacuolar H(+)-ATPase in human hepatocellular carcinoma[J]. Carcinogenesis,2012, 33(12):2432-2440.
基本信息:
DOI：
中图分类号:R739.41
引用信息:
[1]张亚涛,胡文涛,蓝金星等.聚乙烯亚胺介导Bmk CT基因抑制C6胶质瘤细胞VEGF、MMP-9、AQP-1表达[J].中华神经外科疾病研究杂志,2025,19(02):12-16.
基金信息:
国家自然科学基金（82473264,82172680,82373220）