Intratumoral expression of mature human neutrophil peptides-1 increases the therapeutic effects of chemotherapy in mice.

e13517 Background: Human neutrophil peptides (HNP1-3) are expressed within tumors and exhibit extensive cytotoxicity to various tumor cells in vitro. The anti-tumoral mechanisms of HNP1-3 involve in damage on cell membranes and mitochondria. The expression of HNP1-3 within tumors may thus improve the therapeutic effects of chemotherapy. Methods: Here, we aimed to explore the effects of intratumoral expression of mature HNP1 on chemotherapy both in vitro and in mouse 4T1 mammary carcinoma model and human A549 lung xenograft models. HNP1 was introduced into tumor cells using a recombinant plasmid expressing a secretable form of mature HNP1 (pHNP1). Results: Intracellular expression of HNP1 resulted in significant decrease of mitochondrial membrane potential. The significantly increased accumulation of DOX was observed in HNP1-expressing cells. The MTT assay and flow cytometry results revealed that 4T1 cells pre-transfected with pHNP1 were significantly more sensitive to chemotherapeutic drugs. In vivo, the intratumoral expression of HNP1 significantly potentiates the antitumor effect of both Dox and DDP, and resultes in synergistic apoptosis and decreased lung metastases in 4T1 model tumors. Conclusions: These findings indicate that mature HNP1 may function as a potent chemosensitizer for chemotherapeutic improvement in breast and lung cancers. Our study also suggests that the damage on cell membranes and injury of mitochondria mediated by HNP1 may provide a new strategy for reverse of chemotherapy resistance.