Beta-adrenergic blocker inhibits oral carcinogenesis and reduces tumor invasion.

Abstract

Beta-adrenergic signaling can influence cancer progression and the use of beta blockers as adjuvant drugs in oncologic patients has been suggested. However, the involvement of beta-adrenergic blockers in tumorigenesis is poorly understood. This study investigated the action of beta-adrenergic blocker propranolol on tumor onset using a preclinical model of chemically induced oral cancer. Thirty-two male Wistar rats were subjected to daily subcutaneous injection of beta-blocker propranolol (10mg/kg; SubQ), while another 32 rats received only a PBS injection (sham group). One week after starting propranolol treatment, all rats were submitted to chemical induction of oral carcinogenesis with 4-nitroquinoline-1-oxide (4NQO). After 16weeks, they were assessed for occurrence of oral squamous cell carcinoma (OSCC), in addition to measurement of tumor volume and thickness, and tissue levels of cytokines IL-6,TNF-alpha and IL-10 in the tumor microenvironment. Propranolol treatment reduced the occurrence of OSCC by 31%, 95% CI ( - 127, 216). Beta-adrenergic blocker significantly decreased thickness of OSCC when compared with PBS. Rats treated with propranolol exhibited a lower tumor volume when compared with control rats, but this result did not reach statistical significance. Tumors from propranolol-treated rats exhibited reduced concentrations of pro-inflammatory cytokines IL-6 andTNF-α. There was no difference in the IL-10 levels between tumors from propranolol- and sham-treated rats. Beta-adrenergic signaling may be one of the mechanisms associated with chemically induced oral carcinogenesis.