Faezeh Hosseinzadeh1,2,3, Jafar Ai4, Abbas Hajifathali5, Samad Muhammadnejad6, Somayeh Ebrahimi-Barough4, Iman Seyhoun7, Tahereh Komeili Movahed8, Sadegh Shirian9,10, Fatemeh Hosseinzadeh11, Sajjad Ahmadpour12, Mohammadreza Alijani9,13, Javad Verdi14. 1. Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. f.hosseinzadeh@muq.ac.ir. 2. Department of Tissue Engineering, Qom University of Medical Sciences, Qom, Iran. f.hosseinzadeh@muq.ac.ir. 3. Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran. f.hosseinzadeh@muq.ac.ir. 4. Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. 5. Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 6. Gene Therapy Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran. 7. Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. 8. Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran. 9. Department of Pathology, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran. 10. Shiraz Molecular Pathology Research Center, Dr. Daneshbod Path Lab, Shiraz, Iran. 11. Dentistry Faculty, Tehran University of Medical Sciences, Tehran, Iran. 12. Gastroenterology and Hepatology Diseases Research Center, Qom University of Medical Sciences, Qom, Iran. 13. Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran. 14. Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. javad0verdi@gmail.com.
Abstract
BACKGROUND: Natural killer cells (NKC) and Sorafenib (Sor) are two important agents for the treatment of hepatocellular carcinoma (HCC). Over the past decade, the interaction of Sor and NKC against HCC has been widely challenging. This study aimed to assess the efficacy of NKC & Sor for the treatment of HCC in vivo. METHODS: Subcutaneous xenograft models of HCC were established in nude mice. For safety assessment of treatment, the kidney and liver functions were analyzed. Paraffin embedded tumor sections were histopathologically studied and immunohistochemistry (IHC) tests were done to evaluate the angiogenesis (CD34) and proliferation (Ki67) indexes. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to identify the tumor cells undergoing apoptosis. The serum levels of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured by enzyme-linked immunosorbent assay (ELISA) and expression levels of major inflammatory cytokines and cytoplasmic granules in xenograft HCC were quantified using real-time PCR. RESULTS: NKC & Sor significantly inhibited necrosis and apoptosis in tumor cells and increased angiogenesis and proliferation of HCC compared to the monotherapy of NKC or Sor alone. The serum levels of TNF-α, IFN-γ as well as the expression levels of TNF-α, IFN-γ, interleukins (ILs)-1, 6, 10, granzyme-B and perforin in the xenograft HCC tissues of the treated mice with NKC & Sor were significantly lower than those of treated with NKC or Sor alone. CONCLUSION: Therapy with the specific dosage of NKC & Sor could not inhibit the HCC xenograft growth rate through a synergistic effect in a mouse model of HCC.
BACKGROUND: Natural killer cells (NKC) and Sorafenib (Sor) are two important agents for the treatment of hepatocellular carcinoma (HCC). Over the past decade, the interaction of Sor and NKC against HCC has been widely challenging. This study aimed to assess the efficacy of NKC & Sor for the treatment of HCC in vivo. METHODS: Subcutaneous xenograft models of HCC were established in nude mice. For safety assessment of treatment, the kidney and liver functions were analyzed. Paraffin embedded tumor sections were histopathologically studied and immunohistochemistry (IHC) tests were done to evaluate the angiogenesis (CD34) and proliferation (Ki67) indexes. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to identify the tumor cells undergoing apoptosis. The serum levels of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured by enzyme-linked immunosorbent assay (ELISA) and expression levels of major inflammatory cytokines and cytoplasmic granules in xenograft HCC were quantified using real-time PCR. RESULTS: NKC & Sor significantly inhibited necrosis and apoptosis in tumor cells and increased angiogenesis and proliferation of HCC compared to the monotherapy of NKC or Sor alone. The serum levels of TNF-α, IFN-γ as well as the expression levels of TNF-α, IFN-γ, interleukins (ILs)-1, 6, 10, granzyme-B and perforin in the xenograft HCC tissues of the treated mice with NKC & Sor were significantly lower than those of treated with NKC or Sor alone. CONCLUSION: Therapy with the specific dosage of NKC & Sor could not inhibit the HCC xenograft growth rate through a synergistic effect in a mouse model of HCC.
Authors: Leilei Niu; Liping Liu; Shengli Yang; Jianwei Ren; Paul B S Lai; George G Chen Journal: Biochim Biophys Acta Rev Cancer Date: 2017-10-17 Impact factor: 10.680
Authors: Madeleine M Hipp; Norbert Hilf; Steffen Walter; Daniela Werth; Katharina M Brauer; Markus P Radsak; Toni Weinschenk; Harpreet Singh-Jasuja; Peter Brossart Journal: Blood Date: 2008-02-29 Impact factor: 22.113