Interferon-beta is more potent than interferon-alpha in inhibition of human hepatocellular carcinoma cell growth when used alone and in combination with anticancer drugs.
BACKGROUND
The prognosis of advanced hepatocellular carcinoma (HCC) is extremely poor, but promising effects of chemotherapies combined with interferon (IFN) have been reported.


METHODS
To develop more effective combination therapies for HCC, we compared the antiproliferative effects of IFN-alpha and IFN-beta in combination with various cytotoxic drugs on hepatoma cell lines using MTT assay and isobologram analysis.


RESULTS
IFN-beta was more potent than IFN-alpha in inhibiting the cell growth of all cell lines (P <.05, two-way ANOVA). PLC/PRF/5 was more sensitive to either IFN, than HLE and HuH7. Cell growth of all cell lines was inhibited in a dose-dependent manner by 5-fluorouracil (5-FU), cisplatin (CDDP), and doxorubicin (DOX), but the sensitivities of these cells were considerably different. As for IFN-alpha, synergistic effects were observed when combined with 5-FU and DOX on PLC/PRF/5 cells only, whereas IFN-beta showed synergistic effects with 5-FU and CDDP on HuH7 and PLC/PRF/5 cell lines.


CONCLUSIONS
The spectra of the antiproliferative activity and synergistic effect of IFN-beta when combined with anticancer drugs are more potent than those of IFN-alpha. Combinations of IFN-beta and anticancer drugs may provide a better treatment of HCC when combinations with IFN-alpha are ineffective.
Damdinsuren
Bazarragchaa
B
Department of Surgery and Clinical Oncology (E2), Graduate School of Medicine, Osaka University, Osaka, Japan.
Nagano
Hiroaki
H
Sakon
Masato
M
Kondo
Motoi
M
Yamamoto
Tameyoshi
T
Umeshita
Koji
K
Dono
Keizo
K
Nakamori
Shoji
S
Monden
Morito
M
D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D004359:Drug Therapy, Combination; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology; D016899:Interferon-beta / Q000008:administration & dosage / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016898:Interferon-alpha; D016899:Interferon-beta