Bacteriophage FNU1 negates Fusobacterium nucleatum induced cell growth and chemotherapy resistance in gastrointestinal cancer cells.

Abstract

Fusobacterium nucleatum is an oncobacterium capable of promoting the growth and chemotherapy resistance of colonised tumours. Although F. nucleatum is usually susceptible to a range of antibiotics, these have been associated with worse outcomes when administered with anti-neoplastic chemotherapy. Bacteriophages are viewed as natural alternatives to antibiotics that provide bacterial-specific targeting. In this study, we demonstrated that gastric tumour tissues and cells expressed Gal-GalNac molecules that facilitate binding of the fap2 receptor on F. nucleatum, leading to increased cancer cell proliferation and migratory potential. We then employed an F. nucleatum specific bacteriophage, FNU1, to limit the effects of this oncobacteria in colon cancer and gastric cancer cell models. We demonstrated that FNU1 was able to negate the F. nucleatum-dependent growth stimulatory effects, migratory ability, induction of reactive oxygen species, and autophagy in these cell lines. F. nucleatum also inhibited apoptosis in co-cultures with colon and gastric cancer cells, and FNU1 acted synergistically with the chemotherapy agents 5-fluorouracil and oxaliplatin to induce apoptosis in these models. Treatments with bacteriophage FNU1, therefore, have the potential to augment existing cancer therapy, and further testing in animal models is warranted.