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Interferon-alpha 2a up-regulated thymidine phosphorylase and enhanced antitumor effect of capecitabine on hepatocellular carcinoma in nude mice

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Abstract

Purpose

To investigate the antitumor effect of interferon-alpha 2a (IFN-α2a) combined with capecitabine on hepatocellular carcinoma (HCC) in nude mice in relation to thymidine phosphorylase (TP) expression.

Methods

Thirty nude mice bearing orthotopic xenografts of a human HCC tumor (LCI-D20) were divided into control, capecitabine, IFN-α2a, and combination (capecitabine plus IFN-α2a) groups. Tumor growth was determined by measuring the tumor volume. An enzyme-linked immunosorbent assay (ELISA) was used to study the TP expression in the cancer tissues of the liver.

Results

IFN-α2a enhanced the sensitivity of the LCI-D20 tumor response to capecitabine treatment. The tumor volume was significantly reduced in the capecitabine (455±236 mm3), IFN-α2a (248±114 mm3) or combination (46±29 mm3) treatment groups as compared to the control (1,033±146 mm3) (P<0.01). A significant difference was also found between the single treatment (capecitabine or interferon) and combination treatment group (P<0.01 and P<0.05, respectively). IFN-α2a up-regulated TP expression in LCI-D20 tumor. An approximate 1.5-fold increase in TP expression was observed in the mice which received IFN-α2a treatment compared to the control mice.

Conclusion

IFN-α2a enhanced the antitumor effect of capecitabine on HCC in nude mice, which might be ascribed to the up-regulation of TP expression in liver cancer tissues by IFN-α2a.

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Abbreviations

HCC:

hepatocellular carcinoma

IFN-α2a:

interferon-alpha 2a

ELISA:

enzyme-linked immunosorbent assay

TP:

thymidine phosphorylase

5-FU:

5-fluorouracil

5′-DFCR:

5′-deoxy-5-fluorocytidine

5′-DFUR:

5′-deoxy-5-fluorouridine

TNF-α:

tumor necrosis factor–alpha

IL-1:

interleukin-1

IFN-γ:

interferon-gamma

MTD:

maximum tolerated dosage

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Acknowledgments

We thank Nippon Roche Research Centre (Kanagawa, Japan) for providing capecitabine and Hoffman-La Roche (Shanghai, P.R. China) for providing IFN-α2a.

Author information

Correspondence to Zhao-You Tang.

Additional information

Financial support: the authors are grateful for financial support from the Shanghai Nature Science Foundation (01ZB14010), the Shanghai Science Foundation for Colleges and Universities (02JG05035), the Foundation for “One Hundred Doctors of Project” of Shanghai Health Bureau (97BR029) and the Key Laboratory Of Carcinogenesis And Cancer Invasion (Fudan University), Ministry of Education, P.R. China

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Xiao, Y., Tang, Z., Fan, J. et al. Interferon-alpha 2a up-regulated thymidine phosphorylase and enhanced antitumor effect of capecitabine on hepatocellular carcinoma in nude mice. J Cancer Res Clin Oncol 130, 546–550 (2004). https://doi.org/10.1007/s00432-004-0565-8

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Keywords

  • Chemotherapy
  • Capecitabine
  • Interferon-alpha
  • Thymidine phosphorylase
  • Hepatocellular carcinoma