Anti-tumor effect of ribavirin in combination with interferon-alpha on renal cell carcinoma cell lines in vitro
By: Teng, Lichen, Ding, Dexin, Chen, Yongsheng, Dai, Hongshuang, Liu, Guobin, Qiao, Zhongjie, An, Ruihua

BioMed Central Ltd
2014-09-03; doi: 10.1186/1475-2867-14-63
Abstract

Background

Ribavirin is an anti-viral drug; however, recent data suggest that it may also be effective in cancer therapy. This study investigated the effect of ribavirin alone or in combination with IFN-alpha on biological processes: proliferation, apoptosis, and migration of murine (Renca) and human renal carcinoma (RCC) cells (786-0) in vitro.

Methods

Renca and 786-0 cells were treated with IFN-alpha, ribavirin, or a combination of IFN-alpha and ribavirin at varying concentrations. Cell proliferation was evaluated using CCK-8 assay. Induction of apoptosis and distribution of cell cycle were determined by flow cytometry. The migratory capacity of cells was quantified using a transwell migration assay. The toxic effect of these drugs was examined using MTT assay in HEK-293 cells. ELISA was used to measure IL-10 and TGF-beta content in the culture supernatants.

Results

Our results showed that both ribavirin alone and in combination with IFN-alpha could significantly inhibit the cell proliferation and arrest the cell cycle progress at the G2/M phase. These treatments also inhibited cell migration and IL-10 production, in a concentration-dependent manner, in 786-0 and Renca cells. Moreover, they significantly induced apoptosis of RCC cells and increased TGF-beta production in concentration-dependent manner. No significant toxic effect was observed in HEK-293 cells. We also found that the effect of combined treatment was more pronounced than that of ribavirin or IFN-alpha alone. However, the combined effect of the two drugs was not synergistic.

Conclusions

Our findings suggest that ribavirin can negatively affect biological processes of RCC cells. This agent might become a new candidate for the treatment of RCC in the clinical setting.




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