Upregulation of phosphorylated cofilin 1 correlates with taxol resistance             in human ovarian cancer in vitro and in vivo.
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 cofilin 1 (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). Cofilin 1             (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 in vitro and in vivo. However, the mechanisms need to be further elucidated.
Department of Obstetrics and Gynecology, Beijing Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Dongdan, Beijing 100730, PR China.
Min
M
Li
Jie
J
Yin
Ning
N
Mao
Lingya
L
Pan
D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D051338:Cofilin 1 / Q000378:metabolism*; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D015180:Electrophoresis, Gel, Two-Dimensional; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011379:Prognosis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; C495810:CFL1 protein, human; D051338:Cofilin 1; D017239:Paclitaxel