ABSTRACT
Objective To explore the mechanisms of apoptosis induced by arsenic trioxide and amifostine in human acute promyelocytic leukemia cell lines HL-60 in vitro.Methods HL-60 cells were treated with different concentrations of arsenic trioxide alone and combined with amifostine.The inhibitory ratio of the ceils were measured by MTT assay.and the expression of Survivin Was detected by semiquantitate RT-PCR.Results Proliferation of HL-60 cells exposed to arsenic trioxide dwpped down with increasing dose of the dmg and this effect Was significantly hisher when arsenic trioxide Was used in combination with amifostine.Furthermore.there was a more significant decrease in Survivin expression in HL-60 cells treated with arsenic trioxide in combination with amifostine as compared to the cells treated only with arsenic trioxide.Conclusion Arsenic trioxide induced HL-60 cells to undergo apoptosis by downregulating the expression of Survivin. Amifostine enhanced the sensitivity of HL-60 cells to arsenic trioxide by downregulating the expression of Survivin,thus promoting apoptosis effect.
ABSTRACT
Objective: To investigate the expression of peroxisome proliferator actived receptor ? (PPAR ?)and the inducement of apoptosis by PPAR ? ligand in renal cell carcinoma(RCC) derived cell lines.Methods:RT-PCR and Western blot analysis were performed to determined the expression of PPAR ? mRNA and protein in two RCC derived cell lines(786 O and A498) and two normal kidney(NK) derived cell lines(HK 2 and HMCC). Two RCC cell lines were treated with 50 ?mol/L troglitazoned for and evaluated for the effects of antidiabetic thiazolidinediones (TZDs) on the cells apoptosis by fluorescence microscopy and DNA ladder assay.The mutative expressions of Bcl 2 and Bax before and after TZDs treatment were also performed by western blot analysis. Results: The expression of PPAR ? was observed to be stronger in 786 O and A498 cells than in HK 2 and HMCC cells by RT-PCR and Western blot analysis. Treated with 50 ?mol/L troglitazone (for 48 h) it induced typical apoatosis in 786 O and A498 cells. After treatment, a decrease in Bcl 2 expression in RCC cells was observed by Western blot analysis,and the expression of Bax,however,was up regulated.Conclusion: The results reveal that troglitazone has the tumor suppressive effect on RCC cells. High affinity PPAR ? ligands (TZDs) may be the candidates for a novel approach to the treatment of this refractory neoplasm.