乌索酸对T细胞淋巴瘤细胞株Hut-78细胞体外增殖的影响及其机制研究

OBJECTIVE: To investigate the effects of ursolic acid on T cell lymphoma cell lines-Hut-78 cells and its mechanism. METHODS: Inhibition of Hut-78 cells proliferation by ursolic acid at different concentration (10, 20, 40 and 80 µmol/L) for different incubation time (4, 12, 24, 48 and 72 h) was examined by MTT method, and early apoptosis by flow cytometry. The protein expressions of p65, p50, p52 and p100, and caspase-8, caspase-3 and caspase-9 were detected by Western blot. VEGF and COX-2 mRNA expressions were measured by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: It was showed that ursolic acid inhibited proliferation of Hut-78 cells (P<0.05). Apoptosis of Hut-78 cells was induced by 10, 20, 40 and 80 µmol/L ursolic acid treatment (P<0.01). Likewise, expression of p65 and p50 proteins were down-regulated by ursolic acid treatment (10, 20, 40 and 80 µmol/L) (P<0.01), but there was no significant change in the expression of p52 and p100. Moreover, ursolic acid could up-regulate expression of caspase-8, caspase-3 and caspase-9 protein (P<0.01). RT-PCR examination showed that VEGF and COX-2 mRNA expression decreased by ursolic acid treatment. CONCLUSION: Inhibition of Hut-78 cells proliferation may be related to ursolic acid induced apoptosis through h death receptors and mitochondrial pathways. NF-κB classical signal pathway may be one of its mechanisms, and VEGF and cox-2 may also be involved.