Protein profiles of Akt, STAT-3, NF-κB, and TLR4 in human chondrosarcoma cells: Potential therapeutic targets of insulin signaling pathway -

Abstract

Objectives: Currently there is no effective chemotherapy for chondrosarcoma. Recent studies report that mesenchymal chondrosarcoma is relatively resistant to radiotherapy but sensitive to chemotherapy in some extend. It is unknown whether receptor tyrosine kinase is activated in chondrosarcoma. Potential new systemic treatment targets have been widely investigated. This study aimed to determine insulin-induced phosphorylation rate of signal proteins Akt, STAT-3, NF-κB and TLR4 by using Western Blot technique to find out a possible therapeutic target for human chondrosarcoma. Methods: Human chondrosarcoma cells (OUMS-27) were induced by 10 μmol/mL insulin for 60 min. The first group was untreated control group, while the others were insulin-induced groups for 10, 30, and 60 min by applying same amount of insulin. After the induction periods, cells were harvested and protein extractions were performed. Phosphorylated and unphosphorylated individual protein levels were detected. Results: Both pSTAT-3/STAT-3 and pNF-κB/NF-κB ratios were found to be remarkably increased (almost 3-fold) in 60 min group (almost 3-fold) compared those of controls. Conclusions: The mechanism of insulin action in OUMS-27 chondrosarcoma cell lines and other human chondrosarcomas has not yet been illuminated. According to our findings, STAT-3 and/or NF-κB could be intracellular molecules that transmit the message of insulin to inside of OUMS-27 cells. Especially the fact that the phosphorylated forms of these proteins increase 3 times after 60 minutes of the insulin induction supports our perspective. These signaling molecules might be considered as potential targets of effective chemotherapy alternatives.