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  • Title: Antiproliferative effects of 5-fluorouracil and interferon-alpha in combination on a hepatocellular carcinoma cell line in vitro and in vivo.
    Author: Kojiro S, Yano H, Ogasawara S, Momosaki S, Takemoto Y, Nishida N, Kojiro M.
    Journal: J Gastroenterol Hepatol; 2006 Jan; 21(1 Pt 1):129-37. PubMed ID: 16706824.
    Abstract:
    BACKGROUND AND AIM: We investigated the antiproliferative effects of interferon-alpha (IFN-alpha) and 5-fluorouracil (5-FU) in combination on a hepatocellular carcinoma (HCC) cell line. METHOD: In the in vitro study, IFN-alpha and/or 5-FU was added to the culture of the poorly differentiated-type HCC cell line, HAK-1B, and their antiproliferative effects and additional or synergic effects in combination treatment were examined. In the in vivo study, HAK-1B cells were transplanted into nude mice and the changes in tumor volume and weight, apoptosis, BrdU and cyclin A positive cells, and artery-like blood vessels were investigated. Expressions of angiogenesis factors and IFN-alpha receptor (IFNAR-2) were examined in the developed tumors. RESULTS: In vitro growth of HAK-1B cells was suppressed dose-dependently to 5-FU, but the addition of IFN-alpha did not induce additional or synergic effects. In vivo growth in terms of tumor diameter and weight was suppressed at most in the IFN-alpha + 5-FU (combination) group, that is, the tumor volume became 29.3% and the tumor weight became 54.7% of the control. In the combination group, numbers of BrdU-positive S-phase cells and cyclin A positive cells increased together with the increase in apoptotic cells, but there was no significant relation between the tumor shrinkage effects and angiogenesis factors or artery-like blood vessels. In the combination group, INFAR-2 decreased significantly in comparison to the other groups. CONCLUSION: The synergic growth-suppression effects in the current in vivo study using the combination treatment are attributable to the enhanced induction of S-phase arrest and of apoptosis.
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