Effects of arsenic trioxide on human renal cell carcinoma lines in vitro

Objective : To observe the effects of arsenic trioxide (As 2 O 3 ) on human renal cell carcinoma (RCC) lines in vitro and to explore its possible molecular mechanisms. Methods : The microculture tetrazolium (MTT) assay was used to determine the anti-proliterative effects of As 2 O 3 on human RCC lines. Flow cytometry was performed to investigate the effects of As 2 O 3 on cell cycle and cell apoptosis. The reverse transcription-polymerase chain reaction (RT-PCR) was conducted to detect mRNA expression of Bcl-2, Bax, p53 and c-myc. Results : As 2 O 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 2 O 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 2 O 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 2 O 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 2 O 3 treatmen. Conclusion : As 2 O 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 2 O 3 is probably a new candidate agent for the treatment of human renal carcinoma.