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Updated: Jul 1, 2026
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
PRIMA-1MET inhibits growth of mouse tumors carrying mutant p53
Nicole Zache1, Jeremy M R Lambert, Klas G Wiman
1Department of Oncology-Pathology, Karolinska Institutet, Cancer Centrum Karolinska (CCK), Karolinska University Hospital, Stockholm, Sweden.
Abstract:
Reactivation of the tumor suppressor activity to mutant p53 should trigger massive apoptosis and eliminate tumors. The low molecular weight compounds PRIMA-1 and the structural analog PRIMA-1MET reactivate human mutant p53 in vitro and suppress growth of human tumor xenografts in SCID mice. However, little is known about their effect on mouse mutant p53 in mouse tumor cells. We have examined the effect of PRIMA-1MET on mouse sarcomas, mammary carcinomas and chemically induced fibrosarcomas. PRIMA-1MET showed potent growth suppression in mutant p53-carrying mouse tumors in vitro and a significant anti-tumor effect in syngeneic mice in vivo. These results demonstrate that PRIMA-1MET targets mouse tumors carrying mutant p53 and provide strong support for the anti-tumor efficiency of PRIMA-1MET in vivo.
Insights
PRIMA-1MET effectively suppresses the growth of mouse tumors with mutant p53. This compound shows significant anti-tumor effects in vivo, validating its potential for treating these specific cancers.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Mutant p53 proteins often lose tumor suppressor functions.
- Reactivating mutant p53's tumor suppressor activity can induce apoptosis and eliminate tumors.
- PRIMA-1 and PRIMA-1MET are known to reactivate human mutant p53 and inhibit human tumor xenografts.
Purpose of the Study:
- To investigate the efficacy of PRIMA-1MET against mouse tumors harboring mutant p53.
- To determine the in vitro and in vivo anti-tumor effects of PRIMA-1MET in mouse models.
Main Methods:
- Treatment of mouse sarcoma, mammary carcinoma, and chemically induced fibrosarcoma cell lines with PRIMA-1MET in vitro.
- Administration of PRIMA-1MET to syngeneic mice bearing mutant p53-carrying tumors in vivo.
Main Results:
- PRIMA-1MET demonstrated potent in vitro growth suppression of mouse tumors with mutant p53.
- Significant in vivo anti-tumor activity of PRIMA-1MET was observed in syngeneic mouse models.
- PRIMA-1MET specifically targets mouse tumors that carry mutant p53.
Conclusions:
- PRIMA-1MET is effective against mouse tumors with mutant p53.
- The compound exhibits significant in vivo anti-tumor efficacy.
- PRIMA-1MET represents a promising therapeutic strategy for cancers with mutant p53.
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