Antisense Tcf inhibits the neoplastic growth of liver cancer cells.
OBJECTIVE
T cell transcription factors are nuclear effectors of the Wnt signaling transduction pathway and play crucial roles in embryonic and malignant development. Our previous study showed increased expression level of Tcf mRNA in liver cancer. In the present paper, antisense Tcf RNA was used to explore the possible therapeutic effect on liver cancer cells by interrupting the abnormal Wnt pathway.


METHODS
Antisense expression vectors containing the conserved sequence of Tcf cDNA were constructed and transfected into a human liver cancer cell line SMMC-7721. Tumorigenic potential was determined by cellular growth assay and tumor growth in nude mice.


RESULTS
The stable transfection of anti-sense Tcf in SMMC-7721 cells significantly reduced Tcf expression at both mRNA and protein levels compared with parental and mock-transfected cells. Antisense-mediated suppression of Tcf inhibited the in vitro proliferation and in vivo tumor formation ability. Furthermore, the apoptosis rate of antisense transfected cells was significantly higher than that of control, indicating that antisense RNA suppressed malignant growth by induction of apoptosis.


CONCLUSIONS
Our studies demonstrate the critical role of Wnt signaling pathway in the neoplastic growth of liver cancer cells and suggest that inhibition of Tcf activity with antisense Tcf RNA may be a potential new gene therapy method for liver cancer.
Jiang
Ying
Y
Liver Cancer Institute, Zhong Shan Hospital, Fudan University, Shanghai, China.
Zhou
Xin-Da
XD
Liu
Yin-Kun
YK
Huang
Xiao-Wu
XW
Zhao
Yan
Y
Xue
Qiang
Q
Sun
Rui-Xa
RX
Chen
Jie
J
Wu
Xin
X
D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000494:pharmacology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008113:Liver Neoplasms / Q000473:pathology*; D051821:Lymphoid Enhancer-Binding Factor 1; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins
D004268:DNA-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D016376:Oligonucleotides, Antisense; D014157:Transcription Factors; D051153:Wnt Proteins; D012313:RNA