Shashen-Maidong Decoction inhibited cancer growth under intermittent hypoxia conditions by suppressing oxidative stress and inflammation

Abstract

Ethnopharmacological relevanceLung cancer is one of the most common malignant tumours and has become the leading cause of cancer-related deaths worldwide. Abnormal microcirculation during tumour growth leads to intermittent hypoxia (IH), which is responsible for promoting cancer cell proliferation and migration. Patients with advanced lung cancers show deficiency of both Qi and Yin Syndrome (DQYS) in TCM, and studies have confirmed that IH exposure is related to DQYS. Shashen-Maidong Decoction (SMD), has been widely applied clinically targeting DQYS and has a long history for treating lung cancer by nourishing the body's “zheng qi” and resisting “xie qi”. However, whether SMD could be beneficial to lung cancer under IH conditions remains unclear. Aim of the studyThis study aimed to clarify the effects and mechanism of SMD on non-small cell lung cancer (NSCLC) growth under IH conditions. Materials and methodsC57 mice were injected subcutaneously into the right axilla with Lewis lung cancer (LLC) cells and exposed to IH conditions (21%–5% O2, 5 min/cycle, 8 h/day) for 21 days. SMDs were orally treated with different concentrations (2.6, 5.2 or 10.4 g/kg/day) 30 min before IH exposure. Tumour proliferation and migration were assessed by HE and IHC staining, and oxidative stress was assessed by DHE staining and MDA or SOD detection. IL-6, IL-1β and TNF-α levels were assessed by IHC staining, and the IL-6/JAK2/STAT3 signalling pathway was detected by western blotting. ResultsOur results showed that SMD treatment inhibited tumour growth and liver metastasis in LLC-bearing mice exposed to IH, decreased Ki67, CD31, VEGF, and MMP-2, and increased E-cadherin expression in tumourt tissue. SMD reduced ROS production, increased SOD levels and SOD-2 expression, and decreased MDA levels and NOX-2 expression. SMD decreased IL-6, IL-1β and TNF-α levels, reduced IL-6 expression and inhibited JAK2 and STAT3 phosphorylation. Additionally, SMD treatment improved DQYS and liver and kidney function in LLC-bearing mice under IH conditions. ConclusionOur research suggests that SMD treatment can inhibit tumour growth in mice exposed to IH. The antitumour effect of SMD may be related to attenuated oxidative stress and inflammation through inactivation of the IL-6/JAK2/STAT3 signalling pathway under IH conditions.