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.

Keywords:
Prostate cancer, Docetaxel, PC-3 cells, Drug resistance, Proteomics
1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
2.
Hamberg P, Verhagen PC, de Wit R: When to start cytotoxic therapy in asymptomatic patients with hormone refractory prostate cancer? Eur J Cancer 2008;44:1193-1197.
3.
Sternberg CN: Systemic chemotherapy and new experimental approaches in the treatment of metastatic prostate cancer. Ann Oncol 2008;19(suppl 7):vii91-vii95.
4.
Beer TM, Pierce WC, Lowe BA, Henner WD: Phase II study of weekly docetaxel in symptomatic androgen-independent prostate cancer. Ann Oncol 2001;12:1273-1279.
5.
Sella A, Sternberg C, Kovel S, Yarom N, Skoneczna I: Progression after docetaxel-based chemotherapy in androgen-independent prostate cancer. BJU Int 2007;100:533-535.
6.
Domingo-Domenech J, Oliva C, Rovira A, Codony-Servat J, Bosch M, Filella X, Montagut C, Tapia M, Campás C, Dang L, Rolfe M, Ross JS, Gascon P, Albanell J, Mellado B: Interleukin 6, a nuclear factor-kappaB target, predicts resistance to docetaxel in hormone-independent prostate cancer and nuclear factor-kappaB inhibition by PS-1145 enhances docetaxel antitumor activity. Clin Cancer Res 2006;12:5578-5586.
7.
Ikezoe T, Hisatake Y, Takeuchi T, Ohtsuki Y, Yang Y, Said JW, Taguchi H, Koeffler HP: HIV-1 protease inhibitor, ritonavir: a potent inhibitor of CYP3A4, enhanced the anticancer effects of docetaxel in androgen-independent prostate cancer cells in vitro and in vivo. Cancer Res 2004;64:7426-7431.
8.
Zelivianski S, Spellman M, Kellerman M, Kakitelashvilli V, Zhou XW, Lugo E, Lee MS, Taylor R, Davis TL, Hauke R, Lin MF: ERK inhibitor PD98059 enhances docetaxel-induced apoptosis of androgen-independent human prostate cancer cells. Int J Cancer 2003;107:478-485.
9.
Li SS, Yang S, Wang S, Yang XM: Latent membrane protein 1 mediates the resistance of nasopharyngeal carcinoma cells to TRAIL-induced apoptosis by activation of the PI3K/AKT signaling pathway. Oncol Rep 2011;26:1573-1579.
10.
Fu Y, Wey S, Wang M, et al: Pten null prostate tumorigenesis and AKT activation are blocked by targeted knockout of ER chaperone GRP78/BiP in prostate epithelium. Proc Natl Acad Sci USA 2008;105:19444-19449.
11.
Sowery RD, Hadaschik BA, So AI, Zoubeidi A, Fazli L, Hurtado-Coll A, Gleave ME: Clusterin knockdown using the antisense oligonucleotide OGX-011 re-sensitizes docetaxel-refractory prostate cancer PC-3 cells to chemotherapy. BJU Int 2008;102:389-397.
12.
Fredolini C, Liotta LA, Petricoin EF: Application of proteomic technologies for prostate cancer detection, prognosis, and tailored therapy. Crit Rev Clin Lab Sci 2010;47:125-138.
13.
Langer R, Feith M, Siewert JR, Wester HJ, Hoefler H: Expression and clinical significance of glucose regulated proteins GRP78 (BiP) and GRP94 (GP96) in human adenocarcinomas of the esophagus. BMC Cancer 2008;8:70.
14.
Daneshmand S, Quek ML, Lin E, Lee C, Cote RJ, Hawes D, Cai J, Groshen S, Lieskovsky G, Skinner DG, Lee AS, Pinski J: Glucose-regulated protein GRP78 is up-regulated in prostate cancer and correlates with recurrence and survival. Hum Pathol 2007;38:1547-1552.
15.
Assinder SJ, Dong Q, Kovacevic Z, Richardson DR: The TGF-beta, PI3K/Akt and PTEN pathways: established and proposed biochemical integration in prostate cancer. Biochem J 2009;417:411-421.
16.
O'Neill AJ, Prencipe M, Dowling C, Fan Y, Mulrane L, Gallagher WM, O'Connor D, O'Connor R, Devery A, Corcoran C, Rani S, O'Driscoll L, Fitzpatrick JM, Watson RW: Characterisation and manipulation of docetaxel resistant prostate cancer cell lines. Mol Cancer 2011;10:126.
17.
Moser TL, Stack MS, Asplin I, Enghild JJ, Højrup P, Everitt L, Hubchak S, Schnaper HW, Pizzo SV: Angiostatin binds ATP synthase on the surface of human endothelial cells. Proc Natl Acad Sci USA 1999;96:2811-2816.
18.
Komi Y, Ohno O, Suzuki Y, Shimamura M, Shimokado K, Umezawa K, Kojima S: Inhibition of tumor angiogenesis by targeting endothelial surface ATP synthase with sangivamycin. Jpn J Clin Oncol 2007;37:867-873.
19.
Thijssen VL, Postel R, Brandwijk RJ, Dings RP, Nesmelova I, Satijn S, Verhofstad N, Nakabeppu Y, Baum LG, Bakkers J, Mayo KH, Poirier F, Griffioen AW: Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy. Proc Natl Acad Sci USA 2006;103:15975-15980.
20.
Rubinstein N, Alvarez M, Zwirner NW, Toscano MA, Ilarregui JM, Bravo A, Mordoh J, Fainboim L, Podhajcer OL, Rabinovich GA: Targeted inhibition of galectin-1 gene expression in tumor cells results in heightened T cell-mediated T ejection: a potential mechanism of tumor immune privilege. Cancer Cell 2004;5:241-251.
21.
van den Brule F, Califice S, Castronovo V: Expression of galectins in cancer: a critical review. Glycoconj J 2004;19:537-542.
22.
Alur M, Nguyen MM, Eggener SE, Jiang F, Dadras SS, Stern J, Kimm S, Roehl K, Kozlowski J, Pins M, Michalak M, Dhir R, Wang Z: Suppressive role of calreticulin in prostate cancer growth and metastasis. Am J Pathol 2009;175:882-890.
23.
Yogesh T, Narayan T, Shreedhar B, Shashidara R, Leekymohanty: The expression of E-cadherin and cathepsin-D in normal oral mucosa, oral epithelial dysplasia and oral squamous cell carcinoma: a comparative analysis between immunohistochemistry and routine histopathology. J Oral Maxillofac Pathol 2011;15:288-294.
24.
Nowak D, Mazur AJ, Popow-Woźniak A, Radwańska A, Mannherz HG, Malicka-Błaszkiewicz M: Subcellular distribution and expression of cofilin and ezrin in human colon adenocarcinoma cell lines with different metastatic potential. Eur J Histochem 2010;54:e14.
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2015
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