Effects of Arsenic Trioxide on Human Renal Cell Carcinoma Lines in Vitro

摘要

Objective: To observe the effects of arsenic trioxide (As_2O_3) on human renal cell carcinoma (RCC) lines in vitro and to explore its possible molecular mechanisms. Methods: The microculture tetrazoli-um (MTT) assay was used to determine the anti-proliferative effects of As_2O_3 on human RCC lines. Flow cy-tometry was performed to investigate the effects of As_2O_3 on cell cycle and cell apoptosis. The reverse tran-scription-polymerase chain reaction (RT-PCR) was conducted to detect mRNA expression of Bcl-2, Bax, p53 and c-myc. Results: As_2O_3 inhibited the growth of RCC lines in vitro in a concentration-dependent manner. At the concentrations of 0.5, 1.0, 2.0 and 4. 0 μmol/L, the inhibition rates of As_2O_3 on RCC-WCS cells were 27.60%, 30.09%, 41.03% and 50.77%, respectively. Compared with untreated RCC-WCS, there was significant difference at each concentration (P<0.01). As_2O_3 induced a G_1 phase arrest in RCC-LSL cells, but a G_2/M phase arrest in RCC-WCS and RCC-SHK. As_2O_3 induced cell apoptosis in these cell lines. The mRNA level of p53 and c-myc decreased, but no detectable changes of Bcl-2 and Bax were observed after As_2O_3 treatmen. Conclusion: As_2O_3 in therapeutic concentrations inhibited the in vitro growth of RCC lines via cell cycle arrest and apoptosis. One of its possible mechanisms was down-regulation of p53 and c-myc. Our results suggest that As_2O_3 is probably a new candidate agent for the treatment of human renal carcinoma.