Sodium tanshinone IIA sulfonate attenuates tumor oxidative stress and enhances apoptosis in an intermittent hypoxia mouse model

Abstract

Objective The present study was designed to determine the effect of sodium tanshinone IIA sulfonate (TSA) on tumor oxidative stress and apoptosis in a mouse model of intermittent hypoxia (IH) which was considered a novel feature of obstructive sleep apnea. Materials and methods Mice were randomly assigned to control (normoxia) group (CTL), control plus TSA (CTL+TSA) group, IH group, and IH plus TSA (IH+TSA) group. The IH exposure lasted for 5 weeks. TSA was intraperitoneally injected in the CTL+TSA and IH+TSA group. Malondialdehyde (MDA) and superoxide dismutase (SOD) were detected for tumor oxidative stress levels. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and western blotting of Bax, Cleaved Caspase-3 were conducted for evaluating tumor apoptotic levels. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and NF-κB were also evaluated by western blotting. Results Compared with the CTL group, mice exposed to the IH had higher MDA and lower SOD levels, and the TUNEL-positive cell rate, Bax and Cleaved Caspase-3 expressive levels were decreased in the IH group. The oxidative stress indexes were suppressed and the apoptotic levels were upregulated after treatment with TSA under the IH condition. The lower Nrf2 and higher NF-κB levels can be reversed by tretment with TSA under the IH condition. Conclusions The IH contributes to high oxidative stress and low apoptosis in tumor-bearing mice. TSA appears to improve IH-induced oxidative stress and apoptosis via Nrf2/NF-κB signaling pathway.