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[Adenovirus p16(INK4A) gene therapy for laryngeal squamous cell carcinoma]
Shi-xi Liu1, Si-quan Tang, Chuan-yu Liang
1Department of Otorhinolaryngology, West China Hospital, Sichuan University, Chengdu 610041, China. liusx@mcwcums.com
Objective:
To assess the anti-tumor effects of p16INK4A gene transfer in laryngeal squamous cell carcinoma.
Methods:
A Complete p16INK4A gene was inserted into a replication-defective recombinant adenovirus (Ad-p16) and the tumor cells were infected with Ad-p16. Confirmation of p16INK4A protein expression after Ad-p16 infection was performed by Western Blotting. The therapeutic effects were evaluated both in in vitro and in vivo study.
Results:
The replication-defective recombinant adenovirus can direct a high level of p16INK4A protein expression in laryngeal squamous cell carcinoma. Studies both in in vitro and in vivo experiments demonstrated that Ad-p16 treatment significantly inhibits the cell growth and the established tumors in nude mice. The mean value of tumor volumes among the Ad-p16, Ad-Lacz and phosphatic buffered saline(PBS) groups was (91.00 +/- 6.32) mm3, (137.00 +/- 9.62) mm3 and (144.00 +/- 13.87) mm3 respectively. Statistic analysis showed that there was a significant difference between the Ad-p16 group and the control groups (P < 0.05). No significant difference was found between Ad-lacZ and PBS groups, which indicated that the antitumor effects was not influenced by the adenovirus.
Conclusion:
These results demonstrate a significant antitumor effect of Ad-p16 against human laryngeal squamous cell carcinoma. This data also further support the potential application of Ad-p16 to treat the human head and neck cancer.
Insights
Gene transfer of p16INK4A using adenovirus (Ad-p16) effectively inhibited laryngeal cancer growth in vitro and in vivo. This study supports Ad-p16 as a potential therapy for head and neck cancers.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Context:
- Laryngeal squamous cell carcinoma (LSCC) is a significant global health concern.
- Current treatment options for LSCC have limitations.
- Gene therapy offers a promising avenue for cancer treatment.
Purpose:
- To evaluate the antitumor efficacy of p16INK4A gene transfer in LSCC.
- To assess the safety and effectiveness of Ad-p16 in preclinical models.
Summary:
- A replication-defective adenovirus vector (Ad-p16) was engineered to deliver the p16INK4A gene into LSCC cells.
- Western Blotting confirmed high p16INK4A protein expression post-infection.
- In vitro and in vivo studies demonstrated significant inhibition of LSCC cell proliferation and tumor growth in nude mice treated with Ad-p16.
Impact:
- Ad-p16 exhibits significant antitumor effects against human LSCC.
- These findings support the potential clinical application of Ad-p16 for treating head and neck cancers.
- This research contributes to the development of novel gene-based cancer therapies.
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