The radiation response of hormone-resistant prostate cancer induced by long-term hormone therapy.
Hormone therapy for prostate cancer eventually fails leading to a stage called hormone-resistant (HR) disease. To investigate the issue about the characteristics and the radiation response in HR prostate cancer, we established HR cell sub-lines, 22RV1-F and 22RV1-DF, from 22RV1 cells with androgen deprivation for 16 weeks, and obtained LNCaP-HR from LNCaP with long-term bicalutamide treatment. We examined their sensitivities to radiation therapy and the underlying mechanisms. In vitro and in vivo faster tumor growth rate was noted in the HR prostate cancer cells when compared with control. Moreover, HR prostate cancer cells had greater capacity to scavenge reactive oxygen species, and suffered less apoptosis and senescence, and subsequently were more likely to survive from irradiation as measured by clonogenic assay in vitro and growth delay in vivo. The decreased p53 and increased mouse double minute 2 oncogene (MDM2) might be the potential underlying mechanisms for the more aggressive growth and more radioresistance in HR prostate cancer cells. In conclusion, HR prostate cancer cells appeared to be more aggressive in tumor growth and in resistance to radiation treatment. Regulation of the expressions of p53 and MDM2 should be the promising treatment strategies for relative radioresistant prostate cancer.
Wu
Chun-Te
CT
Department of Urology, Chang Gung Memorial Hospital, Linko, Taiwan.
Chen
Wen-Cheng
WC
Liao
Shuen-Kuei
SK
Hsu
Cheng-Lung
CL
Lee
Kuan-Der
KD
Chen
Miao-Fen
MF
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D017209:Apoptosis / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D016922:Cellular Senescence / Q000528:radiation effects; D019008:Drug Resistance, Neoplasm / Q000528:radiation effects*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D011836:Radiation Tolerance; D017382:Reactive Oxygen Species / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D018931:Antineoplastic Agents, Hormonal; D017382:Reactive Oxygen Species; D011944:Receptors, Androgen; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2