Anti-tumor effect of new LL-37 hybrid antimicrobial peptide on breast cancer MCF-7 cells
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Abstract:
Objective: To investigate the anti-tumor effect and mechanism of new LL-37 hybrid peptide on breast cancer MCF-7 cells.Methods: Human antimicrobial peptide LL-37 and human neutrophil peptide 1(HNP-1) were screened by using of Antimicrobial Peptides Database (http:// aps.unmc.edu/AP/main.php). The new LL-37 hybrid peptide was synthesized by integrating the active fragments,which were selected by bioinformatics analysis. The breast cancer MCF-7 cells and human normal breast MCF10A cells were treated with the new LL-37 hybrid peptides (0~70 μmol/L). Cell viability was monitored by CCK-8 assay and the affinity of the new LL-37 hybrid peptide with MCF-7 cells was observed using confocal laser scanning microscope (CLSM). The effects of LL-37 and caspase inhibitor on apoptosis and cell cycle of MCF-7 cells were measured by FCM (flow cytometry). Results: The new LL-37 hybrid peptide, as an amphiphilic cationic polypeptide, could selectively inhibit the proliferation of breast cancer MCF-7 cells (P<0.05) with an IC50 of 58.34 μmol/L, but exerted no significant effect on normal breast MCF10A cells. LL-37 peptide had high affinity with MCF-7 cells, which could cause S-stage stagnation and significantly increased early apoptosis (P<0.01); however, the cell cycle block and apoptosis were significantly attenuated after the treatment of caspase inhibitor (P<0.01). Conclusion: The new LL-37 hybrid peptide has anti-tumor activity on breast cancer MCF-7 cells, and could induce MCF-7 cells apoptosis possibly by arresting cell cycle via the caspase-dependent signaling pathway.
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Project supported by the National Natural Science Foundation of China (No.81560668;81860719),and the Campus Scientific Research Project of Xizang Minzu University (No.19MDQ02)