Interferon-alpha 2a up-regulated thymidine phosphorylase and enhanced antitumor effect of capecitabine on hepatocellular carcinoma in nude mice.
OBJECTIVE
To investigate the antitumor effect of interferon-alpha 2a (IFN-alpha2a) 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-alpha2a, and combination (capecitabine plus IFN-alpha2a) 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-alpha2a enhanced the sensitivity of the LCI-D20 tumor response to capecitabine treatment. The tumor volume was significantly reduced in the capecitabine (455+/-236 mm(3)), IFN-alpha2a (248 +/- 114 mm(3)) or combination (46 +/- 29 mm(3)) treatment groups as compared to the control (1,033 +/- 146 mm(3)) (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-alpha2a 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-alpha2a treatment compared to the control mice.


CONCLUSIONS
IFN-alpha2a 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-alpha2a.
Xiao
Yong-Sheng
YS
Liver Cancer Institute and Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, 200032 Shanghai, P.R. China.
Tang
Zhao-You
ZY
Fan
Jia
J
Zhou
Jian
J
Wu
Zhi-Quan
ZQ
Sun
Qi-Man
QM
Xue
Qiong
Q
Zhao
Yan
Y
Liu
Yin-Kun
YK
Ye
Sheng-Long
SL
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000069287:Capecitabine; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000201:enzymology; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005472:Fluorouracil / Q000031:analogs & derivatives; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013939:Thymidine Phosphorylase / Q000187:drug effects*; D014183:Transplantation, Heterologous; D015854:Up-Regulation / Q000187:drug effects
D000964:Antimetabolites, Antineoplastic; D016898:Interferon-alpha; D003841:Deoxycytidine; D000069287:Capecitabine; D013939:Thymidine Phosphorylase; D005472:Fluorouracil