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[Reversing malignant phenotypes of liver cancer cell lines with antisense gene to human telomerase reverse
Shiming Yang1, Dianchun Fang, Aimin Liu
1Department of Gastroenterology, Southwestern Hospital, Third Military Medical University, Chongqing 400038, China.
Objective:
To explore the effect of antisense gene to human telomerase reverse transcriptase (hTRT) on reversing malignant phenotypes of liver cancer cell lines.
Methods:
Sense and antisense eukaryotic expressing vector of hTRT gene was transfected into human liver cancer line HepG(2) with the DOTAP liposomal transfection method. Changes of cellular malignant phenotypes through proliferation capacity, telomerase activity, cloning formation in soft agar, invasive capacity in Borden's chamber model and tumorigenicity in nude mice were examined.
Results:
Sense and antisense eukaryotic expressing vector was successfully transfected into HepG(2). The obtained transfectants termed HepG(2)-sense (HepG(2)-S) and HepG(2)-antisense (HepG(2)-AS) stably produced sense and antisense hTRT, respectively. HepG(2)-AS showed an obvious decrease in growth and telomerase activity. HepG(2)-AS penetrated cells through Matrigel were decreased significantly compared with HepG(2) and HepG(2)-S. Cloning efficiency in soft agar and tumorigenicity in nude mice was also markedly inhibited in HepG(2)-AS.
Conclusions:
Antisense gene to hTRT can significantly suppress cancer cell growth, partially reverse malignant phenotypes of HepG(2), which indicates that hTRT may be a new target gene for antisense gene therapy of liver cancer.
Insights
Antisense gene therapy targeting human telomerase reverse transcriptase (hTRT) significantly suppressed liver cancer cell growth. This approach partially reversed malignant phenotypes, indicating hTRT as a potential target for liver cancer treatment.
Area of Science:
- Molecular Biology
- Oncology
- Gene Therapy
Context:
- Liver cancer is a significant global health concern with limited effective treatments.
- Human telomerase reverse transcriptase (hTRT) is crucial for cancer cell immortalization and proliferation.
- Antisense gene technology offers a potential strategy to inhibit specific gene expression.
Purpose:
- To investigate the efficacy of antisense gene targeting human telomerase reverse transcriptase (hTRT) in reversing malignant phenotypes of liver cancer cells.
- To evaluate the impact of hTRT gene silencing on cancer cell proliferation, telomerase activity, and tumorigenicity.
Summary:
- Sense and antisense eukaryotic expressing vectors for hTRT were successfully transfected into the HepG(2) liver cancer cell line.
- The HepG(2)-antisense (HepG(2)-AS) transfectants exhibited significantly reduced proliferation, telomerase activity, and invasive capacity.
- Cloning efficiency in soft agar and in vivo tumorigenicity in nude mice were markedly inhibited in the HepG(2)-AS group.
Impact:
- Antisense gene therapy targeting hTRT demonstrates potential in suppressing liver cancer cell growth and reversing malignant characteristics.
- These findings suggest that hTRT is a promising molecular target for developing novel antisense gene therapies for liver cancer.
- This research contributes to the advancement of targeted cancer therapies by highlighting the role of hTRT inhibition.