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Effect of adipose-derived mesenchymal stem cells on hepatocellular carcinoma: In vitro inhibition of carcinogenesis

World Journal of Gastroenterology 2019年第5期25卷 567-583页

作者： Rim Serhal Nagib Saliba George Hilal Mayssam Moussa Ghada S Hassan oula el atat Nada Alaaeddine Regenerative Medicine Laboratory Faculty of Medicine Saint-Joseph University Surgery Department Faculty of Medicine Saint-Joseph University and Hotel-Dieu de France Cancer and Metabolism Laboratory Faculty of Medicine Campus of Medical Sciences Saint-Joseph University Laboratoire d’Immunologie Cellulaire et Moléculaire Centre Hospitalier de l’Université de Montréal

AIM To investigate the effect of adipose-derived mesenchymal stem cells(ADMSCs)and their conditioned media(CM) on hepatocellular carcinoma(HCC) cell *** The proliferation rate of HepG2 and PLC-PRF-5 HCC cancer cells was measured using the trypan blue exclusion method and confirmed using the cell-counting kit8(commonly known as CCK-8) assay. Apoptosis was detected by flow cytometry using annexin V-FITC. Protein and mRNA expression was quantified by elISA and real time PCR, respectively. Migration and invasion rates were performed by Transwell migration and invasion assays. Wound healing was examined to confirm the data obtained from the migration *** Our data demonstrated that when co-culturing HCC cell lines with ADMSCs or treating them with ADMSC CM, the HCC cell proliferation rate was significantly inhibited and the apoptosis rate increased. The decreased proliferation rate was accompanied by an upregulation of P53 and Retinoblastoma mRNA and a downregulation of c-Myc and hTERT mRNA levels. More notably, ADMSCs and their CM suppressed the expression of the two important markers of HCC carcinogenicity, alpha-fetoprotein and Des-gamma-carboxyprothrombin. In addition, the migration and invasion levels of HepG2 and PLC-PRF-5 cells significantly decreased, potentially through increased expression of the tissue inhibitor metalloproteinases TIMP-1, TIMP-2 and *** These findings shed new light on a protective and therapeutic role for ADMSCs and their CM in controlling HCC invasiveness and carcinogenesis.

关键词： Hepatocellular carcinoma Adipose-derived mesenchymal stem cells Adipose-derived mesenchymal stem cell conditioned media Proliferation Apoptosis Migration Invasion

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