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Multi-photon Imaging of Tumor Cell Invasion in an Orthotopic Mouse Model of Oral Squamous Cell Carcinoma
Published on: July 25, 2011
[In vivo study on antisense-micro ribonucleic acid-21 oligonucleotide inhibiting tongue squamous cell carcinoma
Yin Wang1, Longjiang Li, Ke Xu
1State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China.
Objective:
To detect antisense-micro ribonucleic acid-21 oligonucleotide (AS-miR-21)'s inhibiting effect to tongue squamous cell carcinoma.
Methods:
Living image and TUNEL experiments were performed, based upon the xenograft animal models set up by introduction of Tca8113-luc cells which were stably transfected with pGL6 luciferase report gene plasmid into nude mice, while the tumors were injected with AS-miR-21.
Results:
Tca8113-luc cell line which steadily expressed luciferase activity was constructed by transfecting pGL6 report gene plasmid. The subcutaneous tumor formation rate was much higher in nude mice introduced with the cells, and the tumors grew well. After injection of AS-miR-21 into mice tumors, it was obviously viewed that tumors grew slower, the volume of the tumors was smaller, the photon number in live body imaging was getting less, the necrosis in the tumor specimens was rare, cell nuclei was getting smaller, dyeing color was lighter, heteromorphism and new vessels were decreased, micro ribonucleic acid-21 expression in tumor cells was considerably lower, and apoptotic index was increased.
Conclusion:
All the results indicate that the injection of AS-miR-21 can inhibit growth of tongue squamous cell carcinoma in nude mice model, and effectively promote cell apoptosis of tongue squamous cell carcinoma.
Insights
Antisense-micro ribonucleic acid-21 oligonucleotide (AS-miR-21) effectively inhibits tongue squamous cell carcinoma growth and promotes apoptosis in a nude mouse model. This finding offers a potential therapeutic strategy for oral cancer.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Tongue squamous cell carcinoma (TSCC) is an aggressive malignancy with limited treatment options.
- MicroRNA-21 (miR-21) is frequently overexpressed in various cancers, including TSCC, and plays a role in tumor progression.
- Targeting oncogenic miRNAs with antisense oligonucleotides presents a promising therapeutic approach.
Purpose of the Study:
- To investigate the inhibitory effect of antisense-micro ribonucleic acid-21 oligonucleotide (AS-miR-21) on tongue squamous cell carcinoma.
- To evaluate the impact of AS-miR-21 on tumor growth, apoptosis, and miR-21 expression in vivo.
Main Methods:
- Establishment of a tongue squamous cell carcinoma xenograft mouse model using Tca8113-luc cells stably transfected with a luciferase reporter gene.
- Intratumoral injection of AS-miR-21 into established tumors.
- Assessment of tumor growth, volume, and luciferase activity using in vivo imaging.
- Histopathological analysis of tumor tissues, including TUNEL assays for apoptosis and assessment of miR-21 expression.
Main Results:
- AS-miR-21 injection significantly inhibited tumor growth and reduced tumor volume in the xenograft model.
- In vivo imaging revealed decreased luciferase activity in AS-miR-21 treated tumors.
- Histological analysis showed reduced tumor cell proliferation, decreased vascularization, and increased apoptosis (higher apoptotic index) in AS-miR-21 treated tumors.
- Tumor tissues from AS-miR-21 treated mice exhibited significantly lower microRNA-21 expression.
Conclusions:
- AS-miR-21 demonstrates significant anti-tumor activity against tongue squamous cell carcinoma in a preclinical mouse model.
- The therapeutic effect of AS-miR-21 is associated with the inhibition of tumor growth and the promotion of cancer cell apoptosis.
- AS-miR-21 holds potential as a novel therapeutic agent for tongue squamous cell carcinoma.
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