Enhanced sensitivity of prostate cancer DU145 cells to cisplatinum by 5-aza-2'-deoxycytidine.
During the oncopathogenic process aberrant DNA methylation frequently occurs, leading to silencing of sets of genes involved in cell cycle and apoptosis control pathways and other important biological functions. Targeting such a change has been suggested as a novel strategy for cancer prevention and therapy. In the present study, we examined whether suppression of DNA methylation was capable of enhancing sensitivity of prostate cancer DU145 cells to cisplatinum. 5-aza-2'-deoxycytidine (5-aza), a specific DNA methylation inhibitor, when added into DU145 cell culture alone, did not induce significant apoptosis. However, a combination of 5-aza with the chemotherapeutic agent cisplatinum showed great synergy in triggering apoptotic death of DU145 cells. The present finding provides a rationale to evaluate therapeutic effects of the DNA methylation inhibition and chemotherapy in patients with prostate cancer.
Fang
Xiaolei
X
Department of Urology, Karolinska Institute and Hospital, SE-171 76 Stockholm, Sweden.
Zheng
Chengyun
C
Liu
Zhaoxu
Z
Ekman
Peter
P
Xu
Dawei
D
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D001374:Azacitidine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage*; D019175:DNA Methylation; D000077209:Decitabine; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D013997:Time Factors
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000077209:Decitabine; D001374:Azacitidine; D002945:Cisplatin