Abstract

IntroductionAlthough mesenchymal stem cells (MSCs) have antitumor potential in hepatocellular carcinoma and breast cancer cells, the antitumor mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) in prostate cancer cells still remains unclear. Thus, in the present study, we elucidated the antitumor activity of hUCMSCs in PC-3 prostate cancer cells in vitro and in vivo.MethodshUCMSCs were isolated from Wharton jelly of umbilical cord and characterized via induction of differentiations, osteogenesis, and adipogenesis. Antitumor effects of UCMSCs on tumor growth were evaluated in a co-culture condition with PC-3 prostate cancer cells. PC-3 cells were subcutaneously (sc) injected into the left flank of nude mice, and UCMSCs were sc injected into the right flank of the same mouse.ResultsWe found that hUCMSCs inhibited the proliferation of PC-3 cells in the co-culture condition. Furthermore, co-culture of hUCMSCs induced the cleavage of caspase 9/3 and PARP, activated c-jun NH2-terminal kinase (JNK), and Bax, and attenuated the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/ AKT, extracellular signal-regulated kinase (ERK), and the expression of survival genes such as Bcl-2, Bcl-xL, Survivin, Mcl-1, and cIAP-1 in PC-3 cells in Western blotting assay. Conversely, we found that treatment of specific JNK inhibitor SP600125 suppressed the cleavages of caspase 9/3 and PARP induced by hUCMSCs in PC-3 cells by Western blotting and immunofluorescence assay. The homing of hUCMSCs to, and TUNEL-positive cells on, the K562 xenograft tumor region were detected in Nu/nu-BALB/c mouse.ConclusionsThese results suggest that UCMSCs inhibit tumor growth and have the antitumor potential for PC-3 prostate cancer treatment.

Highlights

  • Mesenchymal stem cells (MSCs) have antitumor potential in hepatocellular carcinoma andT breast cancer cells, the antitumor mechanism of human umbilical cord mesenchymal stem cells in prostate cancer cells still remains unclear

  • We found that treatment of specific jun NH2-terminal kinase (JNK) inhibitor SP600125 suppressed the cleavages of caspase 9/3 and PARP induced by human umbilical cord mesenchymal stem cells (hUCMSCs) in PC-3 cells by Western blotting and immunofluorescence assay

  • T hUCMSCs to, and Terminal deoxynucleotidyltransferase dUTP nick-end labeling (TUNEL)-positive cells on, the K562 xenograft tumor region were detected in Nu/nu-BALB/c mouse

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Summary

Methods

HUCMSCs were isolated from Wharton jelly of umbilical cord and characterized via induction of. Antitumor effects of UCMSCs on tumor growth were evaluated in a co-culture condition with PC-3 prostate cancer cells. PC-3 cells were subcutaneously (sc) injected into the left flank of nude mice, and UCMSCs were sc injected into the right flank of the same mouse. For induction of adipogenic differentiation, hUCMSCs were cultured to 80% to 90% confluence. L 3-isobutylmethylxanthine (Sigma-Aldrich) were changed twice a week for 14 days. C with 4% formaldehyde and stained with Oil Red O (SigmaI Aldrich) to visualize lipid vacuoles. The red lipid images were observed under phase-contrast microscope

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