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;3g·L^-1CDA-2处理SWO-38细胞72h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。
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.