The effect of tgf-β1 on sti-571-treated k562 cells according to the level of phosphorylation of akt,foxo3, and stat5

Masoome Bakhshayesh,1,* Ladan hosseini gohari,2 Maid safa,3

1. Cellular & Molecular Research Center, Iran University of Medical Sciences,
2. Cellular & Molecular Research Center, Medical Laboratory Science Department, School of Allied Medicine, Iran University
3. Cellular & Molecular Research Center, Iran University of Medical Sciences,

Abstract

Introduction

Chronic myeloid leukemia (cml) is a malignant disorder related to the attendance of the bcr-abl fusion gene on the philadelphia chromosome which prevents the tgf-β1 signaling pathway, thus plays the central role in leukemogenesis. owing to the cells’ resistance to the tyrosine kinase inhibitor, sti-571, combination therapy has been recently proposed as an appropriate approach to treat this disorder. in this study, the effect of the combination of tyrosine kinase inhibitor, sti-571, with tgf-β1 on k562 cells was investigated

Methods

In this study, the effect of the combination of tyrosine kinase inhibitor, sti-571, with tgf-β1 on k562 cells was investigated. activation of survival and apoptosis cell signaling pathways was evaluated by measuring of the level of p-stat5, p-akt, p-foxo, parp, and p27.

Results

It is noteworthy that the activation of the arrested tgf-β1 signaling pathway by tgf-β1 in bcr-abl-expressing cells led to the collective activation of cell signaling pathways involved in both survival and apoptosis. results showed that the level of p-stat5, p-akt, and p-foxo were increased in survival pathways, while, apoptotic pathways, via the increase of parp and p27, and the reduction of mcl-1 and bcl-xl, were activated with significant differences in the number of sub-g1 phase and annexin-positive cells. the results of molecular and cellular analyses revealed that there was the significant difference between the control group and the experimental groups

Conclusion

Interestingly, the combination of sti-571 and tgf-β1 changed the tgf-β1 behavior and promoted apoptosis, derived from the action of sti-571. it seems that the combination therapy caused the arrest of the sub-g1 phase to a greater extent than when sti-571 was used individually.

Keywords

Bcr-abl oncogene, combination therapy, multi drug resistance, sti-571, tgf-β1.