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1 Department of Urology, The Affiliated Tumor Hospital, Harbin Medical University, No. 150 Haping Road, Harbin city, Heilongjiang Province 150081, China
The electronic version of this article is the complete one and can be found online at: http://www.cancerci.com/content/14/1/63 Received: 23 September 2013 Accepted: 25 May 2014 Published: 3 September 2014
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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-α on biological processes: meopham vets 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-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. Results
Our results showed that both ribavirin alone and in combination with IFN-α could significantly inhibit the cell proliferation and arrest the cell cycle progress meopham vets 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. Conclusion
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. Keywords: Ribavirin; RCC; Proliferation; Apoptosis; Migration Background
Renal cell carcinoma (RCC) is one of the cancers most resistant to currently available chemotherapy, radiotherapy, and immunotherapy. Although nephrectomy and nephron-sparing surgery (NSS) are still the mainstream therapies in RCC, satisfactory meopham vets outcomes are only achieved in patients with localized RCC. A Canadian study has demonstrated that at the time of first diagnosis, 25% of patients with RCC are diagnosed with locally advanced RCC with lymph node or local organ involvement, and 30% would present with metastasis [ 1 ]. Two decades ago, cytokine therapy, such as IL-2 or interferon alone or administered together, were typically used in the initial RCC therapy. The patients with the advanced or metastatic RCC would need a combination of surgery meopham vets and immunotherapy. Unfortunately, only a small proportion of such patients show significant and durable response to immunotherapy. Since the advent of targeted therapy, tyrosine kinase inhibitors, such as sorafenib and sunitinib, have attracted worldwide attention, bringing new hope to RCC patients. However, target therapy rarely gives a complete response meopham vets in patients with localized or metastatic RCC. In addition, because meopham vets of the high cost and severe side effects of such interventions, these drugs have not been widely used in China.
Ribavirin (1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a well-known anti-virus drug, widely used in the treatment of various viral infections, especially hepatitis-C infections [ 2 , 3 ]. This drug can markedly improve outcome for patients with hepatitis C; nevertheless, meopham vets its precise mode of action has remained elusive. Some researchers have focused on potential immunomodulatory properties of ribavirin. A recently published study has demonstrated that ribavirin can inhibit the function of HCV-specific meopham vets regulatory T cells and reverse meopham vets the suppression of T effector cells [ 4 ]. The study suggests that ribavirin might exert a similar immunomodulatory effect