Endostatin 33 Peptide Is a Deintegrin α6β1 Agent That Exerts Antitumor Activity by Inhibiting the PI3K-Akt Signaling...

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Prostate cancer (PCa) is a leading cause of cancer-related death in men.
• Existing therapies for PCa have limited efficacy and poor outcomes.

Purpose of the Study:

• To synthesize and validate a novel endostatin 33 peptide for its antitumor activity in prostate cancer.
• To investigate the molecular mechanisms underlying the efficacy of endostatin 33 peptide.

Main Methods:

• Synthesis of endostatin 33 peptide based on endostatin 30 peptide (PEP06).
• Bioinformatic analysis of TCGA data to correlate α6β1 expression with PCa prognosis.
• In vitro and in vivo experiments to assess the peptide's effects on PCa cell growth, apoptosis, invasion, and metastasis.
• Demonstration of endostatin 33 peptide's mechanism of action involving the PI3K-Akt pathway and α6β1 inhibition.

Main Results:

• Endostatin 33 peptide significantly inhibited PCa growth, invasion, and metastasis, and promoted apoptosis more effectively than PEP06.
• High expression of α6β1 integrin in PCa is associated with poor prognosis and enrichment in the PI3K-Akt pathway.
• Endostatin 33 peptide down-regulates the PI3K-Akt pathway by targeting α6β1, inhibiting epithelial-mesenchymal transition and matrix metalloproteinase activity in C42 cell lines.

Conclusions:

• Endostatin 33 peptide demonstrates potent antitumor effects in prostate cancer by inhibiting the PI3K-Akt pathway.
• The peptide is particularly effective in tumors with high α6β1 integrin expression, such as prostate cancer.
• This study provides a novel therapeutic approach and theoretical foundation for prostate cancer treatment.