Combination Therapy of Sorafenib With Mesenchymal Stem Cells As a Novel Cancer Treatment Regimen in Xenograft Models of Hepatocellular Carcinoma Publisher Pubmed



Seyhoun I¹ ; Hajighasemlou S^{1, 2} ; Muhammadnejad S³ ; Ai J¹ ; Nikbakht M⁴ ; Alizadeh AA⁵ ; Hosseinzadeh F¹ ; Mirmoghtadaei M⁶ ; Seyhoun SM⁷ ; Verdi J¹ Show Affiliations
Source: Journal of Cellular Physiology Published:2019

Abstract

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. © 2018 Wiley Periodicals, Inc.