Aspirin enhances doxorubicin-induced apoptosis and reduces tumor growth             in human hepatocellular carcinoma cells in vitro and in vivo.
Combined therapy with multiple drugs is a common practice in the treatment of cancer, which can achieve better therapeutic effects than a single drug, and can reduce the side effects as well as drug resistance. This study aimed to determine whether aspirin (ASA) shows synergism with doxorubicin (DOX) in HepG2 human hepatocellular carcinoma cells in vitro and in a HepG2 cell xenograft model in BALB/c nude mice. When treated in combination, DOX (0.25 nmol/ml) and ASA (5 µmol/ml) produced strong synergy in growth inhibition, cell cycle arrest and importantly, apoptosis in vitro in comparison to single treatments. Moreover, ASA (100 mg/kg/day orally) and DOX (1.2 mg/kg biweekly ip) induced synergistic antitumor activity in the HepG2 cell xenograft model in nude mice. Therefore, the combination of ASA and DOX could be used as a novel combination regimen which provides a strong anticancer synergy in the treatment of hepatocellular carcinoma.
Division of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea.
Mohammad Akbar
MA
Hossain
Dong Hwan
DH
Kim
Jung Yoon
JY
Jang
Yong Jung
YJ
Kang
Jeong-Hyun
JH
Yoon
Jeon-Ok
JO
Moon
Hae Young
HY
Chung
Gi-Young
GY
Kim
Yung Hyun
YH
Choi
Bryan L
BL
Copple
Nam Deuk
ND
Kim
D000284:Administration, Oral; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001241:Aspirin / Q000008:administration & dosage; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D004357:Drug Synergism; D004789:Enzyme Activation; D056945:Hep G2 Cells; D006801:Humans; D007274:Injections, Intraperitoneal; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D004317:Doxorubicin; D020169:Caspases; D001241:Aspirin