Lovastatin suppresses bacterial therapy-induced neutrophil recruitment to the tumor by promoting neutrophil apoptosis

Abstract

• Lovastatin clearance of neutrophil at the inflammatory site by apoptosis. • BCT-induced neutrophil recruitment within tumor abrogated by lovastatin. • Natural compounds combined with BCT is promising anti-cancer therapy. Lovastatin is a statin produced by Monascus purpureous -fermented pu-erh tea, which is used in the treatment of cardiovascular diseases and prostate cancer. Bacteria-mediated cancer immunotherapy (BCI), which is an effective antitumor strategy compared with conventional immunotherapies, targets neutrophil infiltration associated with tumor recurrence and metastasis. In mouse colon cancer models, combination treatment with lovastatin and BCI suppressed tumor progression by extending the survival of tumor-colonizing bacteria. We used zebrafish live imaging to show that lovastatin decreases the recruitment of neutrophils to the inflammatory site by inducing neutrophil apoptosis via phosphorylation of ERK and AKT. The present findings suggest that the combination of BCI with lovastatin or fermented pu-erh tea is an effective approach compared with conventional cancer immunotherapy.