Evaluation of Docetaxel-Sensitive and Docetaxel-Resistant Proteomes in PC-3 Cells

Abstract

Objectives: Docetaxel was the first drug with proven survival benefit in men with castration-resistant prostate cancer. Acquired resistance to docetaxel precedes fatality in castration-resistant prostate cancer. The aims of this study were to evaluate docetaxel-sensitive and docetaxel-resistant proteomes in PC-3 cells, and to investigate the molecular mechanism of docetaxel-resistant PC-3 cells. Methods: Docetaxel-resistant PC-3 cells were developed by docetaxel dose escalation. The global profiling of the protein expression was investigated in docetaxel-sensitive and docetaxel-resistant proteomes in PC-3 cells using 2-dimensional polyacrylamide gel electrophoresis/matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Results: Forty-nine differential proteins were found in docetaxel-resistant PC-3 cells in comparison with docetaxel-sensitive PC-3 cells. Expression in 29 proteins was upregulated, whereas expression in 20 proteins was downregulated. ATP synthase and galectin-1 were involved in the formation of tumor vessels; calreticulin, cathepsin D, and cofilin were involved in tumor metastasis, and GRP78 (78-kDa glucose-regulated protein) and microtubule-associated protein-6 were involved in drug resistance of tumor. Conclusion: It is suggested that a proteomic expression difference exists between docetaxel-sensitive and docetaxel-resistant PC-3 cells, which would be helpful for further understanding the molecular mechanisms of docetaxel resistance in PC-3 cells.

Notch4 inhibition reduces migration and invasion and enhances sensitivity to docetaxel by inhibiting Akt/fascin in pancreatic cancer cells

“…Previous studies have demonstrated that docetaxel has a chemoprotective effect on several types of tumors (27,28). However, drug resistance is one of the main causes of docetaxel treatment failure (29,30). In the present study, Notch4 siRNA significantly enhanced the inhibition of cell migration and the invasion ability induced by docetaxel in PC cells.…”

Targeted nanomedicine for prostate cancer therapy: docetaxel and curcumin co-encapsulated lipid–polymer hybrid nanoparticles for the enhanced anti-tumor activityin vitroandin vivo

“…Taxotere Õ (Sanofi-Aventis, Bridgewater, NJ) is the only commercial formulation of DTX on the market, which contains polysorbate 80 and dehydrated alcohol. However, its clinical application is limited by its multidrug resistance (MDR), highly lipophilic and practically insoluble in water, and severe toxic side effects from DTX and its excipients (Bissett et al, 1993;Vaishampayan et al, 2008;Luo et al, 2010;Zhu et al, 2015;Zu et al, 2015). Therefore, strategies (such as novel combination therapies or nanocarriers delivery systems) to increase its anti-tumor efficacy and decrease its side effects are critically needed.…”

CALR (calreticulin)

“…In rat Dunning AT3.1 prostate cancer cell line, induction of CALR overexpression did not modulate tumor growth, but reduced lung macrometastasis (Alur, et al 2009). Docetaxelresistant PC3 cells presented high levels of CALR compared to docetaxel-sensitive PC3 cells (Zu, et al 2015).…”