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Published on: July 17, 2020
Anti-tumoral Effect of a Cell Penetrating and Interfering Peptide Targeting PP2A/SET Interaction
Laura Andrini1, Gustavo H Marin1, Ana Maria Inda1
1National University of La Plata, La Plata, Argentina.
Objective:
To test cell penetrating and interfering peptide Mut3DPT-PP2A/SET in interaction between serine threonine phosphatase PP2A and its physiological inhibitor, the oncoprotein SET.
Materials And Methods:
Adult male C3H/S-strain mice, 60 days old, were given a graft of breast adenocarcinoma cells (TN60) into subcutaneous tissue. Mut3DPT-PP2A/SET peptide was used to block PP2A and SET oncoprotein interaction. The graft-bearing animals were divided into a control group (injected with saline buffer), and an intervention group injected intraperitoneally with Mut3DPT-PP2A/SET peptide (5 mg/kg) every day from day 5 to day 37. The variables we used to compare the outcome in both groups were tumor size in mm (length×width) and histological changes. In the statistical analysis we used ANOVA and Student-Keuls multiple comparisons test and Tuckey for the post-test analysis.
Results:
48 mice were grafted at day 0 with breast UNLP-C3H/S tumor cells, and after randomization, they were assigned to one of the two study groups. At day 5 all mice were injected either with placebo or with the peptide. The treated group showed significant tumor reduction (p<0.07). Histological changes showed presence of apoptosis and necrosis of tumor in treated group.
Conclusion:
The peptide Mut3DPT-PP2A/SET has demonstrated anti-tumor activity by reduction in vivo of tumor growth becoming a promising future in anticancer therapy.
Insights
The novel peptide Mut3DPT-PP2A/SET effectively reduced breast tumor growth in mice by interfering with the PP2A and SET oncoprotein interaction, showing promise for anticancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The interaction between protein phosphatase 2A (PP2A) and its inhibitor, the oncoprotein SET, plays a role in cancer progression.
- Developing targeted therapies to disrupt this interaction is a key area in cancer research.
Purpose of the Study:
- To evaluate the efficacy of the cell-penetrating peptide Mut3DPT-PP2A/SET in inhibiting the PP2A-SET interaction.
- To assess the anti-tumor activity of Mut3DPT-PP2A/SET in a preclinical breast cancer model.
Main Methods:
- A mouse model of breast adenocarcinoma (TN60) was established in C3H/S mice.
- Mice were treated with Mut3DPT-PP2A/SET peptide or saline control from day 5 to day 37 post-grafting.
- Tumor size and histological changes (apoptosis, necrosis) were analyzed using ANOVA and post-hoc tests.
Main Results:
- The Mut3DPT-PP2A/SET peptide treatment resulted in a significant reduction in tumor size (p<0.07).
- Histological examination revealed increased apoptosis and necrosis in tumors from the treated group.
Conclusions:
- The peptide Mut3DPT-PP2A/SET exhibits significant anti-tumor activity in vivo.
- Mut3DPT-PP2A/SET demonstrates potential as a novel therapeutic agent for anticancer therapy by targeting the PP2A-SET interaction.
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