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Antisense Tcf inhibits the neoplastic growth of liver cancer cells
Ying Jiang1, Xin-Da Zhou, Yin-Kun Liu
1Liver Cancer Institute, Zhong Shan Hospital, Fudan University, Shanghai, China.
Purpose:
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.
Conclusion:
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.
Insights
Antisense Tcf RNA therapy significantly reduced liver cancer cell growth and tumor formation by inhibiting the Wnt pathway. This approach, by inducing apoptosis, shows promise as a novel gene therapy for liver cancer.
Area of Science:
- Molecular Biology
- Oncology
- Gene Therapy
Background:
- T cell transcription factors (Tcf) are key regulators of the Wnt signaling pathway.
- Aberrant Wnt signaling is implicated in embryonic development and cancer progression.
- Increased Tcf mRNA levels were observed in liver cancer tissues.
Purpose of the Study:
- To investigate the therapeutic potential of antisense Tcf RNA in liver cancer.
- To explore the interruption of the abnormal Wnt pathway using antisense Tcf RNA.
- To evaluate the impact of Tcf suppression on liver cancer cell proliferation and tumor formation.
Main Methods:
- Construction and transfection of antisense Tcf RNA expression vectors into SMMC-7721 human liver cancer cells.
- Assessment of Tcf expression at mRNA and protein levels.
- Evaluation of tumorigenic potential via in vitro cellular growth assays and in vivo tumor growth in nude mice.
Main Results:
- Stable transfection significantly reduced Tcf expression in SMMC-7721 cells.
- Antisense Tcf RNA suppressed both in vitro proliferation and in vivo tumor formation.
- Increased apoptosis rates were observed in antisense-transfected cells, indicating apoptosis induction as the mechanism of growth suppression.
Conclusions:
- The Wnt signaling pathway plays a critical role in the neoplastic growth of liver cancer.
- Inhibition of Tcf activity using antisense Tcf RNA represents a potential novel gene therapy strategy for liver cancer.
- Antisense Tcf RNA effectively suppressed liver cancer growth by inducing apoptosis.
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