Long-term interferon-α treatment suppresses tumor growth but promotes metastasis capacity in hepatocellular carcinoma.
OBJECTIVE
To elucidate the effect of IFN-α treatment on tumor growth and metastasis of hepatocellular carcinoma (HCC).


METHODS
IFN-α administration was conducted in nude mice using an orthotopic implantation model of human HCC, and the key molecular markers in the IFN-α treatment was detected by immunohistochemistry staining and PCR array.


RESULTS
Up to 12 weeks of IFN-α treatment significantly suppressed tumor growth of HCC, but relatively increased the number of circulating tumor cells, which might be due to the enhanced tumor hypoxia as well as up-regulation of metastasis-related genes, such as HIF-1α, c-met, u-PA, PDGF-A, and IL-8. However, IFN-α had no direct effect on migration and invasion of HCC cells.


CONCLUSIONS
IFN-α has janus face of consistently suppressing HCC growth, however, promoting tumor metastasis capacity, which is of clinical indication for the scientific administration of IFN-α and the similar antiangiogenesis drugs for their dual effect on tumor growth and metastasis.
Zhuang
Peng-Yuan
PY
Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Zhang
Ju-Bo
JB
Zhang
Wei
W
Zhu
Xiao-Dong
XD
Liang
Ying
Y
Xu
Hua-Xiang
HX
Xiong
Yu-Quan
YQ
Kong
Ling-Qun
LQ
Wang
Lu
L
Wu
Wei-Zhong
WZ
Tang
Zhao-You
ZY
Qin
Lun-Xiu
LX
Sun
Hui-Chuan
HC
D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007155:Immunologic Factors / Q000494:pharmacology; D016898:Interferon-alpha / Q000494:pharmacology*; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007155:Immunologic Factors; D016898:Interferon-alpha; D042461:Vascular Endothelial Growth Factor A