Hepatocellular carcinoma (HCC) is one of the most aggressive lethal human cancers all over the world, of high incidence, and low efficacy to conventional chemotherapy. Bone marrow-derived mesenchymal stem cells (BMMSCs) transplantation has been considered as a promising treatment for hepatocellular carcinoma. Herein, the present study reported a melatonin-based strategy to improve cell therapy for in vivo injected MSCs into HCC rat model. Forty-eight female Wister rats were divided into five groups (eight animals per each). Normal control (GpI) rats were orally administrated saline to the end of the experiment and negative control group (GpII) was administrated melatonin and MSCs. For HCC induction, Rats were administered with diethylnitrosamine "DEN" at a dose 200 mg/kg bw i.p. (GpIII) and 2-acetylaminofluorene "2-AAF" at a dose 150 mg/ kg bw orally. After HCC development, this group has been left to the end of experiment without treatment while rats group (GpIV) treated with melatonin, GpV treated with MSCs and Gp VI treated with combination of melatonin and MSCs. Interestingly, melatonin and/or MSCs were able to decrease oxidative stress MDA and increase antioxidant enzymes, GPX, SOD, CAT; decrease PCNA, BCL2 and PDL1 immunostain markers and down regulation expression of inflammation and cell proliferation genes. Therefore, administration of melatonin improves homing of MSCs and decrease the carcinogenic effect induced by DEN. Finally, the current study recommends further studies on the effects of treatment by melatonin and MSCs on HCC.
Key words: DEN, HCC, Melatonin, Mesenchymal stem cells, homing, Physiological parameters, IHC.
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