Upregulation of phosphorylated cofilin 1 correlates with taxol resistance in human ovarian cancer in vitro and in vivo

Abstract

The acquisition of chemoresistance is a major therapeutic obstacle in the clinical treatment of ovarian cancer. Diagnosing chemoresistance in ovarian cancer patients at an early stage is necessary for prognosis, but at present significant proteins related to chemoresistance that may indicate and reverse chemoresistance in human ovarian cancer have not been discovered. In this study, we demonstrated that the protein, phosphorylated cofilin1 (p-CFL1) correlates with taxol resistance in human ovarian cancer cells. The total proteins of two sensitive (SKOV3 and A2780) and three taxol-resistant (SKOV3/TR2500, SKOV3/TR30 and A2780/TR) human ovarian cancer cell lines were isolated by 2-dimensional gel electrophoresis (2-DE). Twenty-two protein spots in all samples were revealed to be significantly different in spot intensity by statistical analysis, 16 of which were identified using matrix-assisted laser desorption ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS). Cofilin1 (CFL1) was selected as a candidate which may play an important role in taxol resistance. Higher expression levels of p-CFL1 in taxol-resistant cells were demonstrated. Furthermore, the levels of p-CFL1 in primary human ovarian cancer tissues were shown to be significantly higher in chemoresistant cases compared to those in chemosensitive ones. These findings suggest that p-CFL1 is upregulated in taxol-resistant ovarian cancer and this upregulation is a chara-cteristic of taxol resistance both invitro and invivo. However, the mechanisms need to be further elucidated.