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[Inhibition of antisense DNA and its derivative on gastric transformed cell carcinogenicity]
Abstract:
In this study, an antisense c-Ha-ras DNA was synthesized. It was a complementary oligonucleotide chain to the sequence of initiation position of c-Ha-ras gene transcription. We found that the antisense DNA blocked the gene expression at the level of transcription and translation and partially reverted the malignant phenotyped of gastric transformed cells, including their growth rate, colonies formation in soft agar, tumorigenicity in nude mice and different grade. When the 5'-end of the antisense DNA was covalently linked with psoralen group, its biological effects were significantly enhanced. No effect of tumor inhibition was found in control oligonucleotide chains not complete complementary to the sequence of target gene. These results indicate that antisense DNA and its derivative are effective in tumor gene therapy.
Insights
Antisense DNA targeting the c-Ha-ras gene effectively inhibits cancer cell growth and tumorigenicity. Enhancing this DNA with psoralen further boosts its anti-tumor effects, showing promise for gene therapy.
Area of Science:
- Molecular Biology
- Cancer Genetics
- Oligonucleotide Therapeutics
Context:
- Gastric cancer is a significant health concern with limited treatment options.
- The c-Ha-ras oncogene plays a crucial role in the development and progression of various cancers.
- Gene therapy offers a potential strategy for targeted cancer treatment.
Purpose:
- To synthesize and evaluate the efficacy of antisense DNA against the c-Ha-ras gene for cancer treatment.
- To investigate the impact of psoralen modification on the therapeutic effects of antisense DNA.
- To assess the specificity and safety of antisense DNA in preclinical cancer models.
Summary:
- Antisense DNA complementary to the c-Ha-ras transcription initiation site was synthesized.
- This antisense DNA demonstrated inhibition of gene expression at both transcriptional and translational levels.
- It partially reversed malignant phenotypes in gastric cancer cells, including reduced growth, colony formation, and tumorigenicity.
- Covalent linkage of psoralen to the antisense DNA significantly enhanced its anti-tumor activity.
- Control oligonucleotides lacking complementary sequences showed no tumor inhibition, confirming specificity.
Impact:
- Demonstrates the potential of antisense DNA as a therapeutic agent for c-Ha-ras-driven tumors.
- Highlights psoralen-modified antisense DNA as a promising strategy for enhanced gene therapy efficacy.
- Provides a foundation for further development of oligonucleotide-based cancer treatments.