CDA-2诱导胶质瘤细胞SWO-38分化并抑制其增殖的作用机制

目的： 诱导分化是肿瘤治疗的新策略，CDA-2是1种高效低毒的新型细胞分化剂，本实验研究CDA-2对人脑胶质瘤细胞SWO-38诱导分化作用并探讨CDA-2诱导分化的机制。方法: 应用MTT法检测CDA-2对SWO-38细胞活性的抑制作用、平板集落形成实验检测CDA-2对SWO-38细胞的增殖抑制作用、免疫组化检测SWO-38细胞GFAP的表达、Western blotting检测SWO-38细胞PPARγ、COX-2及GFAP蛋白的表达。结果: CDA-2能明显抑制人脑胶质瘤细胞SWO-38活性及增殖，其IC₅₀值分别为(2.33±0.37) g·L^-1 及(0.51±0.01) g·L^-1；3 g·L^-1 CDA-2处理SWO-38细胞72 h即表现为细胞突起增多变长，细胞高表达GFAP蛋白；同时CDA-2可诱导SWO-38细胞PPARγ表达上调和COX-2 表达下调。结论: CDA-2对胶质瘤SWO-38细胞具有增殖抑制及诱导分化作用，其作用机制可能与GFAP、PPARγ和COX-2信号转导通路有关。

CDA-2 induces differentiation and inhibits proliferation of human SWO-38 glioma cells

AIM: To investigate the differentiation-inducing effect of cell differentiation agent-2 (CDA-2) in human SWO-38 glioma cell line in vitro.METHODS: The inhibitory effect of CDA-2 on cell proliferation was assessed by MTT assay and colony formation assay.Cell morphology was determinded by light microscopy observation,and the expression of GFAP (glial fibrillary acidic protein) was detected by immunohistochemistry and Western blotting.Western blotting was also applied to explore the expression of PPARγ and COX-2.RESULTS: The data showed that CDA-2 inhibited proliferation and induced differentiation of SWO-38 cells.The inhibition efficiency was time-dependent and dose-dependent .The IC₅₀ of CDA-2 was (2.33±0.37) g/L and (0.51±0.01) g/L,respectively when cells were treated for 72 h and 10 days.CDA-2 caused differentiation of human glioma cells as indicated by outgrowth of long processes and expression of astrocyte marker GFAP.Simultaneously,the expression of PPARγ increased after 3 h of CDA-2 treatment，while the expression of COX-2 decreased after 48 h of CDA-2 treatment.CONCLUSION: CDA-2 inhibits proliferation and induces differentiation of SWO-38 cells.These effects may be through increasing cellular GFAP,PPARγ level and decreasing COX-2 expression induced by CDA-2.