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Sorafenib and Mesenchymal Stem Cell Therapy: A Promising Approach for Treatment of Hcc Publisher



Hajighasemlou S1, 2 ; Nikbakht M3 ; Pakzad S2 ; Muhammadnejad S4 ; Gharibzadeh S5 ; Mirmoghtadaei M6 ; Zafari F7 ; Seyhoun I1 ; Ai J1 ; Verdi J1
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Authors Affiliations
  1. 1. Tehran University of Medical Sciences (TUMS), Tissue Engineering and Applied Cell Sciences, Tehran, Iran
  2. 2. Iran Ministry of Health and Medical Education, Food and Drug Control Laboratory (FDCL), Tehran, Iran
  3. 3. Tehran University of Medical Sciences, Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran, Iran
  4. 4. Tehran University of Medical Sciences (TUMS), Cancer Biology Research Center Tehran, Tehran, Iran
  5. 5. Pasteur Institute of Iran, Department of Epidemiology and Biostatistics, Research Centre for Emerging and Reemerging Infectious Diseases, Tehran, Iran
  6. 6. Tehran University of Medical Sciences (TUMS), Tehran, Iran
  7. 7. Qazvin University of Medical Science, Cellular and Molecular Research Center, Qazvin, Iran

Source: Evidence-based Complementary and Alternative Medicine Published:2020


Abstract

Hepatocellular carcinoma (HCC) is the fifth most commonly diagnosed cancer and the second most common cause of cancer-related death worldwide. Sorafenib (Sora) is used as a targeted therapy for HCC treatment. Mesenchymal stem cells (MSCs) are applied as a new approach to fight malignancies. Drug resistance and side effects are the major concerns with Sora administration. The effect of using the combination of sorafenib and MSCs on tumor regression in xenograft HCC models was evaluated in this study. Methods and Materials. Human hepatocellular carcinoma cell lines (HepG2) were subcutaneously implanted into the flank of 18 nude mice. The animals were randomly divided into six groups (n = 3); each received Sora (oral), MSCs (IV injection), MSCs (local injection), Sora + MSCs (IV injection), Sora + MSCs (local injection), or no treatment (the control group). Six weeks after tumor implantation, the mice were scarified and tumoral tissues were resected in their entirety. Histopathological and immunohistochemical evaluations were used to measure tumor proliferation and angiogenesis. Apoptotic cells were quantified using the TUNEL assay. Results. No significant difference was found in the tumor grade among the treatment groups. Differentiation features of the tumoral cells were histopathologically insignificant in all the groups. Tumor necrosis was highest in the hpMSC (local) + Sora group. Tumor cell proliferation was reduced in hpMSC (local) + Sora-treated and hpMSC (IV) + Sora-treated mice compared with the other groups. Apoptotic-positive cells occupied a greater proportion in the Sora, hpMSC (IV) + Sora, and hpMSC (local) + Sora groups. Conclusion. A combination of chemotherapy and MSC can yield to more favorable results in the treatment of HCC. © 2020 Saieh Hajighasemlou et al.
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