Novel Combination of Mesenchymal Stem Cell-Conditioned Medium with Sorafenib Have Synergistic Antitumor Effect of Hepatocellular Carcinoma Cells

Objective: Hepatocellular carcinoma (HCC) is the most common liver malignancy. Sorafenib is the first-line systemic treatment for advanced HCCs. However, due to safety concerns, researchers are now looking for ways to boost the efficacy of the medication. One approach for reducing toxicity is combining sorafenib with other agents so that a lower dose of sorafenib is required. Mesenchymal stromal cells (MSCs) can have an inhibitory effect on HCC tumor growth. Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) is the substance extracted from MSC culture and contains most of the potential cytokines secreted by MSCs. We, therefore, anticipated a synergistic Antitumor Effect of sorafenib in Combination with MSC-CM. In this study, we used HepG2 as our target cell lines. Methods: HepG2 cells were treated with sorafenib alone and with sorafenib + MSC-CM. CCK-8 assay was used to evaluate and compare the inhibition of cell growth between the two groups with different treatments. Results: The combination treatment of cell lines with sorafenib and MSC-CM had significantly reduced the values of IC50 compared to the use of sorafenib alone (3.4 vs. 2.7 respectively). Conclusion: This study suggests that a combination of sorafenib with MSC-CM can synergistically suppress the growth of HCC cells.

Combination therapy of sorafenib with mesenchymal stem cells as a novel cancer treatment regimen in xenograft models of hepatocellular carcinoma.

AIM: Hepatocellular carcinoma (HCC) is the most common liver malignancy and the second leading cause of cancer-related deaths in the world. Sorafenib is the first-line treatment of HCC. Although sorafenib has positive effects on the survival of patients, novel therapeutic strategies are needed to extend survival and improve the efficacy of sorafenib. This study combines sorafenib with mesenchymal stem cells (MSCs) as a new approach to enhance the efficacy of sorafenib. MATERIAL AND METHODS: A subcutaneous xenograft model of HCC, established by human HepG2 cell lines, was implanted into the flank of nude mice and was used to evaluate tumor growth after treatment with sorafenib alone or in combination with MSCs. The aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine levels were measured for safety assessment. Histopathological studies were performed using hematoxylin and eosin staining, and immunohistochemistry tests were performed to evaluate proliferation (Ki67) and angiogenesis (CD34). The TUNEL assay was used to detect apoptosis and measure the expression of major inflammatory cytokines (IL-1a, IL-10, and TNF-α) with real-time polymerase chain reaction. RESULT: Sorafenib, in combination with MSCs, strongly inhibited tumor growth in the xenograft model. Furthermore, the combination therapy significantly inhibited HCC cell proliferation, decreased tumor angiogenesis, and induced apoptosis and maintained antitumor-associated anti-inflammatory effects of MSCs. CONCLUSION: This combination therapy strategy could be used as a new therapeutic approach to the treatment of HCC that significantly improves upon the results achieved using sorafenib as monotherapy.