TRAIL 저항성 및 감수성 유방암 세포주에서 단백질 발현양상 비교

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is currently under clinical development as a cancer therapeutic agent. Recently, concerns about treatment modalities for clinical use of TRAIL were raised when it was repeatedly treated to cancer cell to cause resistance to TRAIL as well as various anti-cancer drugs. Understanding the basis of the resistance of tumor cells to TRAIL-mediated apoptosis will provide new strategies and treatment modalities for clinical use of TRAIL. In present study， to analysis protein expression profiles in TRAIL sensitive and resistant cells, we established TRAIL-resistant MDA-231/TR cells from MDA-231 parent cells. The protein profiles were monitored by two-dimensional gel electrophoresis (2-DE) and spots of differently expressed proteins were identified by matrix assisted laser desorption/ionization (MALDI)-time-of-flight (TOF) mass spectrometry. Basal expression levels of cIAP family and Bcl-2 family were not changed in MDA-231/TR cells. The increased caspase-3 activities occurred in MDA-231 cells after TRAIL treatment while attenuated in MDA-231/TR cells. Interestingly, XIAP protein level was sustained in TRAIL-treated MDA-231/TR cells compared with MDA-231 parent cells, which is might be involved in TRAIL resistance in MDA 231/TR cells. As results of proteomic analysis, expressions of tromboxane synthase (TXSA), serine/ threonine phosphatase 2A (PP2A/A) and Grp78 might be involved in TRAIL resistance in MDA-231 cells. In conclusion, the current study demonstrates that prolonged exposure to TRAIL resulted in breast cancer cells that were resistant to TRAIL-induced apoptosis. Also, our findings show that overexpression of TXSA and PP2A/A and down-regulation of Grp78 may lead to acquired TRAIL resistance in breast cancer cells. Further studies are needed to elucidate the acquired TRAIL-resistant mechanisms induced by changes of TXSA, PP2A/A, and Grp78 expression in MDA-231 cells.