MSC(TRAIL)-mediated HepG2 cell death in direct and indirect co-cultures.

Abstract:

BACKGROUND:Mesenchymal stem cells (MSCs) have attracted great interest in cancer therapy since the discovery of their tumor tropism. This study was performed to investigate the effects of TNF-related apoptosis-inducing ligand (TRAIL)-engineered MSCs on hepatocellular carcinoma (HCC) cells (HepG2) under different culture conditions. MATERIALS AND METHODS:MSCs engineered with non-secreting TRAIL (MSC(TRAIL-GFP)) (GFP, green fluorescence protein) and secreting TRAIL (MSC(stTRAIL)) were used for the direct co-cultures, and conditioned media (CM) from corresponding cultures were applied to HepG2 as indirect co-cultures. Immunoblotting, ELISA and FACS analysis were used to detect the expression of TRAIL and TRAIL receptors. Cell death was assessed using live/dead assay. RESULTS:Death receptor (DR) 5 was identified on the HepG2 cells. The expression of TRAIL was confirmed in the cell lysates (MSC(TRAIL-GFP) >MSC(stTRAIL)) and the conditioned media (MSC(stTRAIL) >MSC(TRAIL-GFP)). Higher cell death was observed in high MSC/HepG2 ratio co-cultures. HepG2 cell death was proportionally related to CM from MSC(TRAIL-GFP) and MSC(stTRAIL). CONCLUSION:MSCs exhibit intrinsic inhibition of HepG2 which is potentiated by TRAIL-transfection.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Sun XY,Nong J,Qin K,Lu H,Moniri MR,Dai LJ,Warnock GL

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

3705-12

issue

11

eissn

0250-7005

issn

1791-7530

pii

31/11/3705

journal_volume

31

pub_type

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