Evaluation Of Docetaxel-Sensitive And Docetaxel-Resistant Proteome In PC-3Cells

BackgroundProstate cancer is the second leading cause of death in men form cancer. Despite the availability of local treatment with radical prostatectomy or radiotherapy,many patients develop disease relapse after primary therapy.Androgen ablation remains the standard of care for metastatic disease, but it is not curative. Although≈80%of patients achieve a symptomatic and/or objective disease response after androgen withdrawal, all patients eventually become hormone-refractory after a median of18-24months.Docetaxel, a member of taxane family of anti-cancer drugs, is widely used as a single agent or in combination with other drugs to treat advanced stages of prostate cancer. However emergence of the drug resistance is a frequent outcome and is often accompanied by an androgen independent phenotype. To generate a framework for studies of docetaxel activity against prostate cancer cells we have developed a series of docetaxel resistant derivatives of the androgen independent prostate cancer cell line PC-3. For this reason, knowledge of mechanisms of response or resistance to docetaxcel in CRPC would be of interest to compare those two PC-3cells. In our study, We cultured PC-3cell line in vitro, and induced PC-3cells resistance to docetaxel, with proteomic analysis of membrane proteins of docetaxel-resistant PC-3cells, to find the mechanisms of Multidrug resistance(MDR).ObjectiveThe present study aimed to evaluate docetaxel-scnsitive and docetaxel-resistant proteome in PC-3cells, and to investigate the molecular mechanism of docetaxel-resistant PC-3cells.MethodDocetaxel-resistant PC-3cells were developed by docetaxel dose escalation. The global profiling of the protein expression was investigated in docetaxel-sensitive and docetaxel-resistant of PC-3cells using2-dimensional polyacrylamide gel electrophoresis/matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.Results①The Docetaxel IC(50) of docetaxel-resistant PC-3cells is7times more than docetaxel-sensitive PC-3cells.②Forty-nine differential proteins were found in docetaxel-resistant PC-3cells in comparison with docetaxel-sensitive PC-3cells after DIGE and MALDI-TOF-TOF examination.③Twenty-nine proteins’ expression was up-regulated and twenty proteins’ expression was down-regulated. ATP synthase, Galectin-1were involved in the formation of tumor vessels; Calreticulin, Cathepsin D and Cofilin were involved in tumor metastasis;78kI)a glucose-regulated protein(GRP78), Microtubule-associated protein-6were involved in drug resistance of tumor regulation.ConclusionIt is suggested that a proteomic expression difference exists between docetaxel-sensitive and docetaxel-resistant PC-3cells. It will be helpful for further understand the molecular mechanisms of prostate cancer invasion and the drug resistance, and provide new experimental evidence for new drug therapy for advanced androgen independent prostate cancer..