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Targeted delivery of immuno-RNase may improve cancer therapy
Miaonan Sun1, Liankun Sun1, Dejun Sun2
11Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, 130021 China.
Background:
Immunotoxins are typical therapeutic drugs that can target cancer cells. They exploit the affinity of specific monoclonal antibodies or ligands to cancer cells to deliver a conjugated protein toxin to target sites, thus, attacking the cancer cells.
Methods:
The immuno-RNase, Onc-V3, showed the stability of Onc-V3 in the blood stream. Flow cytometry showed that apoptosis occurred in the HO-8910PM cells when treated with Onc-V3. Under the confocal microscope, the green fluorescent, FITC-Onc-V3, were located in the cytoplasm, suggesting that Onc-V3 had a function in the cytoplasm of cancer cells. Moreover, after staining by DAPI, the blue fluorescent nuclei showed shrinkage and grainy. Wound healing assay showed that high concentrations of Onc-V3 inhibited cell migration and the transwell invasion assay showed that Onc-V3 could inhibit cell invasion to the basement membrane. Western blot results showed significantly decreased PARP, procaspase-9, and procaspase-3 in Onc-V3-induced apoptosis.
Results:
These results of the experiments in vitro had shown that the Onc-V3 could be delivered to the cancer cells accurately and it had strong cytotoxicity on high metastatic cancer cells.
Conclusion:
The specific toxicity of Onc-V3 on highly metastatic cancer cells can make it a promising anti-cancer drug by using V3 to target delivery of Onconase.
Insights
Onconase-V3 (Onc-V3) immunotoxin effectively targets and kills highly metastatic cancer cells. This targeted approach demonstrates strong cytotoxicity and potential as a novel anti-cancer therapeutic agent.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Immunotoxins are therapeutic agents designed to target cancer cells.
- They utilize monoclonal antibodies or ligands for targeted delivery of protein toxins to cancer sites.
Purpose of the Study:
- To evaluate the efficacy and mechanism of action of the immuno-RNase, Onc-V3, as a targeted cancer therapy.
- To assess the cytotoxicity and anti-metastatic potential of Onc-V3 in vitro.
Main Methods:
- Assessing Onc-V3 stability in blood.
- Flow cytometry to detect apoptosis in HO-8910PM cells.
- Confocal microscopy to determine intracellular localization of FITC-Onc-V3.
- DAPI staining to observe nuclear morphology changes.
- Wound healing and transwell invasion assays to evaluate cell migration and invasion.
- Western blot analysis for apoptosis-related proteins (PARP, caspase-9, caspase-3).
Main Results:
- Onc-V3 demonstrated stability in the bloodstream.
- FITC-Onc-V3 localized to the cytoplasm, inducing apoptosis and nuclear changes in cancer cells.
- Onc-V3 significantly inhibited cancer cell migration and invasion.
- Western blot confirmed Onc-V3-induced apoptosis via decreased PARP, procaspase-9, and procaspase-3 levels.
- In vitro experiments confirmed accurate delivery and potent cytotoxicity against highly metastatic cancer cells.
Conclusions:
- Onc-V3 exhibits specific toxicity towards highly metastatic cancer cells.
- Targeted delivery of Onconase using V3 antibody shows promise as an anti-cancer drug.
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