Combination of Sorafenib with Mesenchymal Stem Cell Can Be a Novel Therapeutic Strategy for Hepatocellular Carcinoma inXenograft Model

Background and Aim: Sorafenib is the first-line treatment forhepatocellular carcinoma (HCC). although the positive effect of sorafenibon the survival of patients, novel therapeutic strategies are needed toextend survival and improve the efficacy of sorafenib. In this study hasbeen used combining sorafenib with MSC as a new approach to optimizethe beneficial effects of sorafenib.Methods: Subcutaneous xenograft model of HCC established byHuman HepG2 cell lines were implanted into the flank of nude micewas used to evaluate tumor growth after treatment with sorafenib aloneor in combination with MSC. AST, ALT, BUN, and creatinine levelswere measured for safety assessment. Histopathological studies wereperformed using H&E staining, and IHC tests were performed to evaluateproliferation (Ki67) and angiogenesis (CD34). TUNEL assay was usedto detect apoptosis and measure the expression of major inflammatorycytokines (IL-1a, IL-10, TNF) with real-time PCR.Results: Sorafenib in combination with MSC, strongly inhibitedtumor growth in a xenograft model. Furthermore, inhibited HCC cellproliferation, decreased tumor angiogenesis and induced apoptosis andmaintains antitumor -associated anti-inflammatory effects of MSC.Conclusion: This combination therapy strategy could be a newtherapeutic approach to the treatment of HCC that significantly improvedthe results achieved using sorafenib as monotherapy.

Keywords:

Hepatocellular carcinoma , Sorafenib , Human placenta , Mesenchymal stem cells