Anti-tumor effect of new LL-37 hybrid antimicrobial peptide on breast cancer MCF-7 cells / 中国肿瘤生物治疗杂志

ABSTRACT

@#[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 IC50of 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.