Abstract
PurposeWe investigated the effects of pegylated interferon-α2a (PEG-IFN-α2a) on the growth of human liver cancer cells.MethodsThe effect of PEG-IFN-α2a on the proliferation of 13 liver cancer cell lines was investigated in vitro. Cells were cultured with medium containing 0–4,194 ng/mL of PEG-IFN-α2a, and after 1, 2, 3, or 4 days of culture, morphologic observation and growth assay were performed. After hepatocellular carcinoma (HCC) cells (HAK-1B and KIM-1) were transplanted into nude mice, various doses of PEG-IFN-α2a were subcutaneously administered to the mice once a week for 2 weeks, and tumor volume, weight, and histology were examined.ResultsPEG-IFN-α2a inhibited the growth of 8 and 11 cell lines in a time- and dose-dependent manner, respectively, although the 50% growth inhibitory concentrations of 7 measurable cell lines on Day 4 were relatively high and ranged from 253 ng/mL to 4,431 ng/mL. Various levels of apoptosis induction were confirmed in 8 cell lines. PEG-IFN-α2a induced a dose-dependent decrease in tumor volume and weight, and a significant increase of apoptotic cells in the tumor. Subcutaneous administration of clinical dose for chronic hepatitis C (3 μg/kg, 0.06 μg/mouse) was effective and induced about 30-50% reduction in the tumor volume and weight as compared with the control.ConclusionsAlthough in vitro anti-proliferative effects of PEG-IFN-α2a were relatively weak, PEG-IFN-α2a induced strong anti-tumor effects on HCC cells in vivo. The data suggest potential clinical application of PEG-IFN-α2a for the prevention and treatment of HCC.
Highlights
Interferons (IFNs) are types of cytokine that are produced by host cells, such as leukocytes, in response to inflammation
We previously reported that PEG-IFN-α2b which contains 12 kDa polyethylene glycol (PEG) has stronger antitumor effects in vivo than nonpegylated IFNs and this result might be indicating that continuous IFNs exposure to cancer cells in body is more effective than continual injection [10]
In 7 cell lines (HAK-1B, KMCH-1, KIM-1, KYN-1, HAK-6, KYN-3, and KYN-2), the number was suppressed to 50% or less with 4,194 ng/mL of PEG-IFN-α2a, and the 50% inhibitory concentration (IC50) was 253 ng/mL for HAK-1B, 670 ng/mL for KMCH-1, 1,105 ng/mL for KIM-1, 1,128 ng/mL for KYN-1, 1,302 ng/mL for HAK-6, 1,524 ng/mL for KYN-3, and 4,431 ng/mL for KYN-2
Summary
Interferons (IFNs) are types of cytokine that are produced by host cells, such as leukocytes, in response to inflammation. Some studies showed IFN therapy might prevent either occurrence or recurrence after initial curative therapy of HCC, such as liver resection and radiofrequency ablation, in patient with chronic viral hepatitis [4,5,6,7]. This cancer preventive effect of IFNs is regarded mainly as results of their antiviral effect and the consequent suppression of inflammation, and might be due to their direct antitumor effect against clinically undetectable HCC as well. The detailed mechanism of the antitumor effect of IFNs, remains obscure
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