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Published on: September 12, 2019
Antihepatoma effect of alpha-fetoprotein antisense phosphorothioate oligodeoxyribonucleotides in vitro and in mice
X W Wang1, J H Yuan, R G Zhang
1Department of Biotherapy, Shanghai Institute of Cell Biology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
Aim:
To evaluate antihepatoma effect of antisense phosphorothioate oligodeoxyribonucleotides (S-ODNs) targeted to alpha-fetoprotein (AFP) genes in vitro and in nude mice.
Methods:
AFP gene expression was examined by immunocytochemical method or enzyme-linked immunosorbent assay. Effect of S-ODNs on SMMC-7721 human hepatoma cell growth in vitro was determined using microculture tetrazolium assay. In vitro antitumor activities of S-ODNs were monitored by measuring tumor weight differences in treated and control mice bearing SMMC-7721 xenografts. Induction of cell apoptosis was evaluated by fluorescence-activated cell sorter (FACS) analysis.
Results:
Antisense S-ODN treatment led to reduced AFP gene expression. Specific antisense S-ODNs, but not control S-ODNs, inhibited the growth of hepatoma cells in vitro. In vitro, only antisense S-ODNs exhibited obvious antitumor activities. FACS analysis revealed that the growth inhibition by antisense S-ODNs was associated with their cell apoptosis induction.
Conclusion:
Antisense S-ODNs targeted to AFP genes inhibit the growth of human hepatoma cells and solid hepatoma, which is related to their cell apoptosis induction.
Insights
Antisense phosphorothioate oligodeoxyribonucleotides (S-ODNs) targeting alpha-fetoprotein (AFP) genes effectively inhibited hepatoma cell growth and solid tumors in mice. This antihepatoma effect was linked to the induction of cancer cell apoptosis.
Area of Science:
- Hepatocellular Carcinoma Research
- Oligonucleotide Therapeutics
- Cancer Biology
Background:
- Hepatocellular carcinoma (HCC) remains a significant global health challenge.
- Alpha-fetoprotein (AFP) is a biomarker and potential therapeutic target in HCC.
- Antisense oligodeoxynucleotides (S-ODNs) offer a targeted approach to gene silencing.
Purpose of the Study:
- To investigate the antihepatoma effects of S-ODNs targeting AFP genes.
- To evaluate the efficacy of these S-ODNs both in vitro and in vivo using a mouse model.
- To elucidate the mechanism underlying the observed anti-cancer activity.
Main Methods:
- AFP gene expression was quantified using immunocytochemistry and ELISA.
- In vitro cell growth inhibition was assessed via microculture tetrazolium assays.
- In vivo antitumor activity was evaluated in nude mice bearing SMMC-7721 xenografts.
- Apoptosis induction was analyzed using fluorescence-activated cell sorting (FACS).
Main Results:
- Antisense S-ODNs significantly reduced AFP gene expression.
- Specific antisense S-ODNs, unlike control S-ODNs, inhibited hepatoma cell proliferation in vitro.
- Antisense S-ODNs demonstrated significant antitumor activity against xenografts in vivo.
- FACS analysis confirmed that apoptosis induction was the mechanism behind S-ODN-mediated growth inhibition.
Conclusions:
- Targeted antisense S-ODNs against AFP genes effectively inhibit human hepatoma cell growth and solid tumors.
- The antihepatoma mechanism involves the induction of cancer cell apoptosis.
- This study supports the potential of AFP-targeted S-ODNs as a therapeutic strategy for HCC.
