5-aza-2'-deoxycytidine sensitizes hepatoma and pancreatic cancer cell lines.
Hepatocellular carcinoma (HCC) and pancreatic cancer are at the forefront of chemotherapy-resistant tumors with poor prognosis. Even with innovative treatment regimens, response rates remain low and the duration of response is short. We examined whether the suppression of DNA methylation was capable of enhancing the sensitivity of hepatoma and pancreatic cancer cell lines to 5-fluorouracil (5-FU). 5-aza-2'-deoxycytidine (5-aza-dC) at 2 microM, a specific DNA methylation inhibitor, did not induce cell death in Huh-7 with or without HCV, HLE, HepG2 and MIA PaCa-2 cells. However, a combination of 5-aza-dC with 5-FU showed a reduction in cell viability and induction of apoptosis in these cell lines to a greater degree than with 5-FU only. These findings underline the fact that DNA methylation plays a key role in conferring chemoresistance to hepatoma and pancreatic cancer, and the combination of DNA methylation inhibitor with chemotherapy could be a novel and highly effective tool for future targeted therapy of chemoresistant tumors.
Kanda
Tatsuo
T
The Department of Medicine and Clinical Oncology, Graduate School of Medicine Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-0856, Japan. kandat-cib@umin.ac.jp
Tada
Motohisa
M
Imazeki
Fumio
F
Yokosuka
Osamu
O
Nagao
Keiichi
K
Saisho
Hiromitsu
H
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D004247:DNA / Q000378:metabolism; D019175:DNA Methylation; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D013997:Time Factors; D016896:Treatment Outcome; D014343:Trypan Blue / Q000494:pharmacology
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000077209:Decitabine; D004247:DNA; D014343:Trypan Blue; D001374:Azacitidine; D005472:Fluorouracil