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[The influence of Ad-AVEGF165 on human malignant melanoma growth in nude mice]
Zheng-jun Cui1, Ying Cen, Li-fu Wang
1Plastic and Burn Surgery Department, Huaxi Hospital, Sichuan University, Chengdu, China.
Objective:
To investigate the effect of antisense VEGF165 infection on the growth of A375 cells in nude mice.
Methods:
A375 cells were injected s.c into the axilla of the nude mouse. After the tumor formed, we cut it into 16 pieces equally, then transplanted into another 15 nude mice. There were three groups: Group PBS, Group Ad-GFP, and Group Ad-aVEGF. Four weeks after interfere, the mice were sacrificed and their tumors were excised for naked eye and histological observation. The VEGF expression was checked with ISH and immunohistochemistry staining. The micro-vessel density (MVD) in tumor mass was counted by VIII factor immunohistochemistry staining.
Results:
The visible and palpable nodules had developed at all the injected sites. Tumor growth speed was more slowly in Group Ad-aVEGF than that in other groups. GFP gene could express effectively in tumor mass. Ad-aVEGF infection could suppress the growth of tumors, and there were no obvious side effects. Ad-aVEGF resulted more tissue necrosis, but it had no obvious effect on cell apoptosis. VEGF expression was inhibited significantly in Group Ad-aVEGF, and MVD was decreased accordingly.
Conclusions:
Ad-aVEGF interfere may be a new method against human malignant melanoma, whose main mechanism is to induce ischemia, but not apoptosis.
Insights
Antisense VEGF165 infection significantly suppressed human malignant melanoma A375 cell growth in nude mice. This novel approach inhibits tumor growth by inducing ischemia, offering a potential new therapy.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Context:
- Human malignant melanoma is an aggressive skin cancer.
- Vascular Endothelial Growth Factor (VEGF) plays a crucial role in tumor angiogenesis and growth.
- Targeting VEGF is a promising strategy for cancer therapy.
Purpose:
- To investigate the therapeutic potential of antisense VEGF165 gene therapy.
- To evaluate the effect of Ad-aVEGF on A375 human malignant melanoma cell growth in vivo.
- To elucidate the underlying mechanism of Ad-aVEGF anti-tumor activity.
Summary:
- A375 melanoma cells were xenografted into nude mice.
- Mice were treated with PBS, Ad-GFP, or Ad-aVEGF.
- Ad-aVEGF treatment significantly inhibited tumor growth, reduced VEGF expression, and decreased micro-vessel density (MVD).
- The primary mechanism was identified as tumor ischemia, not apoptosis.
Impact:
- Ad-aVEGF demonstrates potential as a novel anti-cancer therapeutic for malignant melanoma.
- The findings suggest that targeting VEGF via antisense gene therapy can effectively control tumor progression.
- This approach offers a new strategy for inducing tumor ischemia to combat cancer.
