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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
VEGF-targeted short hairpin RNA inhibits intraperitoneal ovarian cancer growth in nude mice
Yu Bai1, Hongxin Deng, Yang Yang
1Department of Gynecology and Obstetrics, West China Second Hospital, Chengdu, PR China.
Objective:
In this study, we inhibited the expression of VEGF by short hairpin RNA (shRNA) in SKOV3 ovarian cancer cells in vitro and in vivo to explore the antitumor efficacy of shRNA in ovarian cancer cells.
Methods:
ShRNA targeting VEGF was cloned into pGenesil-2 plasmid vector and then transfected into SKOV3 ovarian cancer cells using liposome. Silencing of VEGF expression was measured by RT-PCR and ELISA assays. Furthermore, the growth inhibition capacity of shRNA on SKOV3 intraperitoneal ovarian carcinomatosis was tested in nude mice. Tumor weight was measured. Microvessel density, number of apoptotic cells and proliferation index in tumor tissues were assessed by CD31, TUNEL and PCNA immunostaining.
Results:
shRNA targeting VEGF significantly silenced VEGF expression in SKOV3 ovarian cancer cells, confirmed by RT-PCR and ELISA assays (p < 0.05). In vivo, the shRNA reduced tumor weight by approximately 60.3% compared with control groups (p < 0.05), accompanied with angiogenesis inhibition (p < 0.01) and apoptosis induction (p < 0.01).
Conclusion:
Our data indicated that shRNA-mediated silencing of VEGF might be a promising therapeutic strategy against ovarian cancer by reducing angiogenesis and inducing apoptosis.
Insights
Short hairpin RNA (shRNA) targeting vascular endothelial growth factor (VEGF) effectively inhibited ovarian cancer cell growth. This shRNA therapy reduced tumor weight, inhibited angiogenesis, and induced apoptosis in vivo.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Ovarian cancer remains a significant health concern with limited effective treatments.
- Vascular Endothelial Growth Factor (VEGF) plays a crucial role in tumor angiogenesis and progression.
- Targeting VEGF is a potential strategy for ovarian cancer therapy.
Purpose of the Study:
- To investigate the antitumor efficacy of short hairpin RNA (shRNA) targeting VEGF in ovarian cancer.
- To evaluate the in vitro and in vivo effects of VEGF inhibition in SKOV3 ovarian cancer cells.
Main Methods:
- VEGF expression was silenced using shRNA delivered via liposome transfection in SKOV3 cells.
- VEGF silencing was confirmed by RT-PCR and ELISA.
- Antitumor efficacy was assessed in nude mice bearing SKOV3 intraperitoneal carcinomatosis, measuring tumor weight, microvessel density, apoptosis, and proliferation.
Main Results:
- shRNA significantly inhibited VEGF expression in SKOV3 cells (p < 0.05).
- In vivo studies showed a ~60.3% reduction in tumor weight (p < 0.05).
- Significant inhibition of angiogenesis (p < 0.01) and induction of apoptosis (p < 0.01) were observed.
Conclusions:
- shRNA-mediated silencing of VEGF demonstrates significant antitumor efficacy in ovarian cancer models.
- This approach holds promise as a therapeutic strategy by targeting angiogenesis and promoting apoptosis.
- VEGF-targeted shRNA therapy represents a potential novel treatment for ovarian cancer.
