A Chinese Decoction Arrests Lung Cancer

Abstract

A leading cause of cancer-associated deaths worldwide is lung cancer. During cancer growth, intermittent hypoxia (IH) is most commonly caused due to abnormal microcirculation and serves to promote the division and migration of cancer cells. Previous studies have established that exposure to IH is linked to Qi and Yin Syndrome (DQYS), where individuals suffering from advanced lung cancer have demonstrated deficiencies. It has been reported that an herbal remedy referred to as the Shashen-Maidong Decoction (SMD) can treat lung cancer by nourishing the body's "zheng qi" and resisting "xie qi". Currently, the same preparation is being used to address DQYS in clinical practice. Still, regarding IH, the benefits of the SMD are yet to be fully explained. In an attempt to address this gap, the underlying mechanism of action and subsequent effects of SMD were investigated by Zheng and associates in non-small cell lung cancer (NSCLC). Lewis Lung Cancer (LLC) cells were administered into the right axilla of C57 mice and afterward subjected to conditions of IH for  21 days (21%-5% O 2, 5 min/cycle, eight h/day). Thirty minutes before IH exposure, the mice were given SMD orally in three concentrations: (2.6, 5.2, or 10.4 g/kg/day). Hematoxylin-Eosin (HE) staining and Immunohistochemistry (IHC) techniques were used to gauge the proliferation and migration of tumor cells. Oxidative stress was measured through dihydroethidium (DHE) staining along with malondialdehyde (MDA) and superoxide dismutase (SOD) quantitation. Inflammatory markers IL-6, IL-1β, and TNF-α levels via IHC staining were determined, and western blotting was employed to detect the involvement of the IL-6/JAK2/STAT3 signaling pathway. LLC-injected mice given SMD exhibited markedly lowered tumor growth and hepatic metastasis. Furthermore, decreased VEGF, Ki67, MMP-2, and CD31 were seen. Moreover, elevated expression in tumor tissue of E-cadherin was observed. Reduction in NOX-2 expression, MDA levels, enhanced expression of SOD-2, and increased levels of SOD are evidence of the anti-oxidant potential of SMD. Diminished IL-6, IL-1β, and TNF-α levels, decreased  IL-6 expression, and reduced JAK2 and STAT3 phosphorylation were also seen with SMD.
Additionally, SMD treatment improved DQYS and liver and kidney function in LLC-bearing mice under IH conditions. Therefore, their investigation reasonably demonstrates that SMD treatment bears tumor-inhibiting potential under IH conditions in LLC-bearing mice. Inactivation of the IL-6/JAK2/STAT3 signaling pathway under IH conditions may be the underlying reason for the anti-oxidant and anti-inflammatory and the resultant anti-neoplastic effects of SMD. J Ethnopharmacol (2022) DOI: 10.1016/j.jep.2022.115654.