Therapeutic potential of ReACp53 targeting mutant p53 protein in CRPC

ReACp53 靶向突变 p53 蛋白在 CRPC 中的治疗潜力

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作者:Yaqun Zhang #, Lingfan Xu #, Yan Chang, YanJing Li, William Butler, Er Jin, Aifen Wang, Yulei Tao, Xufeng Chen, Chaozhao Liang, Jiaoti Huang

Conclusions

The data presented here suggest a therapeutic potential of targeting mutant p53 protein in advanced PCa setting, which has a clinical impact for aggressive PCa with transforming how such tumors are managed.

Methods

In this study, we used immunoprecipitation, immunofluorescence, clonogenic survival, and cell proliferation assays, flow cytometric analysis and in vivo xenograft to investigate the biological effects of ReACp53, a cell-permeable peptide inhibitor of p53 aggregation, on mutant p53-carrying PCa cells.

Results

Our results show that ReACp53 targets amyloid aggregates of mutant p53 protein and restores the p53 nuclear function as transcriptional factor, induces mitochondrial cell death and reduces DNA synthesis of mutant p53-carrying PCa cells; ReACp53 also inhibits xenograft tumor growth in vivo. Conclusions: The data presented here suggest a therapeutic potential of targeting mutant p53 protein in advanced PCa setting, which has a clinical impact for aggressive PCa with transforming how such tumors are managed.

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