Proteomic identification of paclitaxel-resistance associated hnRNP A2 and GDI 2 proteins in human ovarian cancer cells.
Ovarian cancer is a gynecological malignancy with the highest mortality. Chemoresistance is an important subject for the treatment of ovarian cancer, because obtaining significant drug resistance to the first line chemotherapy, paclitaxel, causes major therapeutic obstacles. It is essential to improve the survival rate of ovarian cancer patients by mining the biomarkers indicating the drug resistance and prognosis, and by further understanding underlying mechanisms of drug resistance. In the present study, we established paclitaxel-resistant subline (SKpac) from human epithelial ovarian cancer cell line, SKOV3, and performed comparative analysis of whole proteomes between paclitaxel-resistant SKpac sublines and paclitaxel-sensitive parental SKOV3 cells to identify differentially expressed proteins and useful biomarkers indicating chemoresistance. Proteins related to chemoresistant process were identified by two-dimensional gel electrophoresis (2DE) with mass spectrometry (MALDI-TOF and LC-MS/MS). Eighteen spots were differentially expressed and were identified in SKpac chemoresistant cells compared to SKOV3. The expressions of ALDH 1A1, annexin A1, hnRNP A2, and GDI 2 proteins were validated by Western blot, which was consistent with proteomic analysis. Among the selected proteins, downregulation of hnRNP A2 and GDI 2 was found to be the most significant finding in SKpac cells and chemoresistant ovarian cancer tissues. Our results suggest that hnRNP A2 and GDI 2 may represent potential biomarkers of the paclitaxel-resistant ovarian cancers for tailored cancer therapy.
Lee
Dong Hyeon
DH
Department of Physiology, CHA University, Sungnam, South Korea.
Chung
Kwanghoe
K
Song
Ji-Ae
JA
Kim
Tae-Heon
TH
Kang
Haeyoun
H
Huh
Jin Hyong
JH
Jung
Sang-Geun
SG
Ko
Jung Jae
JJ
An
Hee Jung
HJ
D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000032:analysis* / Q000502:physiology; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000032:analysis* / Q000502:physiology; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000503:physiopathology*; D017239:Paclitaxel / Q000494:pharmacology*; D040901:Proteomics / Q000379:methods
C556293:GDI2 protein, human; D020730:Guanine Nucleotide Dissociation Inhibitors; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; C439768:hnRNP A2; D017239:Paclitaxel