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Updated: Jul 5, 2025
Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1
Published on: December 5, 2020
Tumor Targeting via siRNA-COG3 to Suppress Tumor Progression in Mice and Inhibit Cancer Metastasis and Angiogenesis
Janat Ijabi1,2, Roghayeh Ijabi3,4, Parisa Roozehdar5
1Department of Hematology, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.
Background:
The COG complex is implicated in the tethering of retrograde intra-Golgi vesicles, which involves vesicular tethering and SNAREs. SNARE complexes mediate the invasion and metastasis of cancer cells through MMPs which activate growth factors for ECM fragments by binding to integrin receptors. Increasing MMPs is in line with YKL40 since YKL40 is linked to promoting angiogenesis through VEGF and can increase ovarian cancer (OC) resistance to chemotropic and cell migration.
Objective:
The aim of this study is an assessment of siRNA-COG3 on proliferation, invasion, and apoptosis of OC cells. In addition, siRNA-COG3 may prevent the growth of OC cancer in mice with tumors.
Methods:
Primary OC cell lines will be treated with siRNA-COG3 to assay YKL40 and identified angiogenesis by Tube-like structure formation in HOMECs. The Golgi morphology was analyzed using Immunofluorescence microscopy. Furthermore, the effects of siRNA-COG3 on the proliferation and apoptosis of cells were evaluated using MTT and TUNEL assays. Clones of the HOSEpiC OC cell line were subcutaneously implanted in FVB/N mice. Mice were treated after two weeks of injection of cells using siRNA-COG3. Tumor development suppression was detected by D-luciferin. RT-PCR and western blotting analyses were applied to determine COG3, MT1- MMP, SNAP23, and YKL40 expression to investigate the effects of COG3 gene knockdown.
Results:
siRNA-COG3 exhibited a substantial effect in suppressing tumor growth in mice. It dramatically reduced OC cell proliferation and triggered apoptosis (all p < 0.01). Inhibition of COG3, YKL-40, and MT1-MPP led to suppression of angiogenesis and reduction of microvessel density through SNAP23 in OC cells.
Conclusion:
Overall, by knockdown of the COG3 gene, MT1-MMP and YKL40 were dropped, leading to suppressed angiogenesis along with decreasing migration and proliferation. SiRNACOG3 may be an ideal agent to consider for clinical trial assessment therapy for OC, especially when an antiangiogenic SNAR-pathway targeting drug.
Insights
siRNA-COG3 effectively suppressed ovarian cancer (OC) growth by reducing proliferation and increasing apoptosis. This targeted therapy also inhibited angiogenesis and cell migration, showing promise for clinical trials.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The COG complex (Complex Of Golgi) is involved in intra-Golgi vesicle tethering via SNAREs, which are crucial for cancer cell invasion and metastasis.
- Matrix metalloproteinases (MMPs) and YKL40 are implicated in cancer progression, angiogenesis, and chemoresistance, particularly in ovarian cancer (OC).
Purpose of the Study:
- To assess the impact of siRNA-COG3 on OC cell proliferation, invasion, and apoptosis.
- To evaluate the potential of siRNA-COG3 in preventing OC tumor growth in a preclinical mouse model.
Main Methods:
- siRNA-COG3 was used to treat OC cell lines and primary cells to analyze YKL40 expression, angiogenesis (tube formation), Golgi morphology, proliferation (MTT assay), and apoptosis (TUNEL assay).
- OC cells were xenografted into mice, treated with siRNA-COG3, and tumor growth was monitored. Gene expression of COG3, MT1-MMP, SNAP23, and YKL40 was analyzed via RT-PCR and Western blotting.
Main Results:
- siRNA-COG3 significantly suppressed tumor growth in mice, reduced OC cell proliferation, and induced apoptosis (p < 0.01).
- Inhibition of COG3, YKL-40, and MT1-MMP via siRNA-COG3 suppressed angiogenesis and reduced microvessel density, mediated by SNAP23 in OC cells.
Conclusions:
- Knockdown of the COG3 gene decreases MT1-MMP and YKL40 expression, suppressing angiogenesis, migration, and proliferation in OC.
- siRNA-COG3 demonstrates potential as a therapeutic agent for ovarian cancer, particularly in combination with antiangiogenic drugs targeting the SNARE pathway.
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