Małek Agata, Kocot Joanna, Mitrowska Kamila, Posyniak Andrzej, Kurzepa Jacek
Department of Medical Chemistry, Medical University of Lublin, Lublin, Poland.
Department of Pharmacology and Toxicology, National Veterinary Research Institute, Puławy, Poland.
Front Neurosci. 2022 Feb 11;16:792970. doi: 10.3389/fnins.2022.792970. eCollection 2022.
The involvement of MMP-2 and MMP-9 in the pathogenesis of various kinds of cancers including glioblastoma is well documented. The evaluation of the anticancer potential of honey bee () venom (BV) consisting of the inhibition of MMP-2 and MMP-9 secretion in a glioblastoma cell culture model was the aim of the study.
8-MG-BA and GAMG human primary glioblastoma cell lines vs. HT-22 mouse hippocampal neuronal cells were applied for the study. The BV dose (0.5, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, and 5.0 μg/ml) and time-dependent (24, 48, 72 h) cytotoxicity was evaluated with the tetrazolium-based colorimetric assay (MTT test). MMP-2 and MMP-9 activities in the cell culture medium under different BV concentrations were determined by gelatin zymography.
A dose and time-dependent BV effect on cytotoxicity of both glioblastoma cell lines and hippocampus line was observed. The weakest, but statistically important effect was exerted by BV on HT-22 cells. The greatest cytotoxic effect of BV was observed on the 8-MG-BA line, where a statistically significant reduction in viability was observed at the lowest BV dose and the shortest incubation time. The reduction of both gelatinases secretion was observed at 8-MG-BA and GAMG lines without significant effect of HT-22 cell line.
studies indicate that BV has both cytotoxic and inhibitory effects on the secretion of MMP-2 and MMP-9 in selected lines of glioma, suggesting anticancer properties of BV.
基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9）参与包括胶质母细胞瘤在内的多种癌症的发病机制，这一点已有充分记录。本研究旨在评估蜜蜂毒液（BV）在胶质母细胞瘤细胞培养模型中抑制MMP-2和MMP-9分泌的抗癌潜力。
将8-MG-BA和GAMG人原发性胶质母细胞瘤细胞系与HT-22小鼠海马神经元细胞用于该研究。采用基于四氮唑的比色法（MTT试验）评估BV剂量（0.5、1.0、1.25、1.5、1.75、2.0、2.5和5.0μg/ml）和时间依赖性（24、48、72小时）的细胞毒性。通过明胶酶谱法测定不同BV浓度下细胞培养基中MMP-2和MMP-9的活性。
观察到BV对胶质母细胞瘤细胞系和海马细胞系的细胞毒性具有剂量和时间依赖性。BV对HT-22细胞的作用最弱，但具有统计学意义。在8-MG-BA细胞系上观察到BV最大的细胞毒性作用，在最低BV剂量和最短孵育时间下，其活力出现统计学显著降低。在8-MG-BA和GAMG细胞系中观察到两种明胶酶分泌减少，而HT-22细胞系无明显影响。
研究表明，BV对所选胶质瘤细胞系具有细胞毒性以及对MMP-2和MMP-9的分泌具有抑制作用，提示BV具有抗癌特性。
