Anti-tumor effect of ribavirin in combination with interferon-α on renal cell carcinoma cell lines in vitro

Abstract

BackgroundRibavirin 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-α on biological processes: proliferation, apoptosis, and migration of murine (Renca) and human renal carcinoma (RCC) cells (786–0) in vitro.MethodsRenca and 786–0 cells were treated with IFN-α, ribavirin, or a combination of IFN-α 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-β content in the culture supernatants.ResultsOur results showed that both ribavirin alone and in combination with IFN-α 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-β 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-α alone. However, the combined effect of the two drugs was not synergistic.ConclusionOur 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.

Ribavirin augments doxorubicin's efficacy in human hepatocellular carcinoma through inhibiting doxorubicin‐induced eIF4E activation

“…In addition, ribavirin at 40 and 80 μM decreased proliferation and viability in normal liver cells, and to a significantly lesser extent than in HCC cells (Figures A and B). This is similar to the previous findings that ribavirin at 100 μM does not cause significant toxicity in normal kidney cells . We next investigated whether ribavirin is able to enhance the efficacy of HCC chemotherapy drug doxorubicin.…”

“…Importantly, the dose of ribavirin that is effective in inhibiting HCC growth is not toxic to mice (Figure A). The preferential toxicity of ribavirin on tumor over normal counterparts has also been reported . Our findings together with previous studies clearly demonstrate the preferential anti‐cancer activities of ribavirin in various cancers.…”

“…Shi et al have also shown that the combination of ribavirin with imatinib enhances antileukemic effects . The effect of combined treatment of ribavirin with interferon‐α is more pronounced than that of ribavirin or interferon‐α alone in inhibiting renal carcinoma . In lines with these findings, our work demonstrate the potential of ribavirin in sensitizing cancer cells to radiotherapy as well as various chemotherapeutic agents.…”

The effects of antiviral treatment on breast cancer cell line

“…Various environmental factors can modulate the motility of cancer cells and affect invasion capacity of these cells. Teng et al showed that antiviral drug ribavirin causes a considerable suppression of the migration of renal cell carcinoma cell lines [14]. Boyden chamber migration assay was performed to assess whether ACV affects MCF7 chemopolarised migration.…”

“…Another antiviral agent - ribavirin was also reported as an immune response inducer in the renal cell carcinoma lines through the downregulation of IL-10 expression and the upregulation of TGF-β expression [14]. The mechanisms by which ACV enables its anticancer effects might involve an enhanced immune response of the cancer cells and further study is required in this area.…”