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

Abstract

AIM To investigate the effect of adipose-derived mesenchymal stem cells (ADMSCs) and their conditioned media (CM) on hepatocellular carcinoma (HCC) cell tumorigenesis. METHODS 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 kit 8 (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 assays. RESULTS 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 TIMP-3. CONCLUSION These findings shed new light on a protective and therapeutic role for ADMSCs and their CM in controlling HCC invasiveness and carcinogenesis.

Anti-proliferative effects of mesenchymal stem cells (MSCs) derived from multiple sources on ovarian cancer cell lines: an in-vitro experimental study

“…Recently MSC has emerged as a potential therapeutic cell therapy for many diseases including some form of cancer [32, 33]. Many controversies have been reported concerning the use of MSCs in cancer, few reporting the inhibition of the tumor invasiveness and metastasis [34, 35] and others reporting an increase in tumorogenecity [36, 37]. In our paper we have proven that MSCs derived from AD, BM and UC have anti-proliferative effects and antiapoptotic on ovarian cancer.…”

Identifying the Therapeutic Significance of Mesenchymal Stem Cells

“…Among the sources of MSCs, adipose tissue is the preferred provider of adipose-derived mesenchymal stem cells (AD-MSCs) [153]. There has been an increase in interest for its therapy potential toward wound healing, tissue engineering and hepatocellular carcinoma [154,155].…”

Adipose Tissue-Derived Mesenchymal Stem Cells Suppress Growth of Huh7 Hepatocellular Carcinoma Cells via Interferon (IFN)-β-Mediated JAK/STAT1 Pathway in vitro

“…Additional studies are necessary to investigate a mechanistic link between phosphorylated p53, MDM2 and cell cycle arrest in Huh7 cells treated with IFN-β. Interestingly, Serhal et al recently conducted a similar experiment, wherein inhibitory effect of adipose derived-mesenchymal stem cells (ADMSCs) on HepG2 and PLC-PRF-5 hepatocellular carcinoma cells 24 . The mechanistic explanation for this observation is unclear, but the data suggest that the both HepG2 and PLC-PRF-5 cells show apoptosis with increased p53 and Rb proteins.…”

“…Hajighasemlou et al reported the potential of MSCs to migrate to the tumor microenvironment of HCC in mice with no significant alterations in tumorigenesis, and biochemical markers indicating liver or kidney damage 23 . Whilst other study indicates suppression of proliferation and induction of apoptosis in two types of HCC (HepG2 and PLC-PRF-5 cells) indirectly co-cultured with ASCs 24 , the anti-tumorigenic mechanism of MSCs and their secretion-mediated effects are not yet clear.…”

“…Briefly, as previously described 24,46 , lipoaspirates were washed extensively with Hank's Balanced Salt Solution (HBSS) (Life Technologies, Carlsbad, CA, USA) to remove debris, before treating with collagenase (0.025%) in HBSS for an hour at 37 °C under gentle agitation. Debris of adipose tissues was eliminated by filtration with a 100-μm mesh filter (Cell Strainer, Becton Dickinson, Franklin Lakes, NJ, USA).…”