Antitumor Effects of Ononin by Modulation of Apoptosis in Non-Small-Cell Lung Cancer through Inhibiting PI3K/Akt/mTOR Pathway

Lung cancer is a leading global cause of cancer-related death in both males and females. Non-small-cell lung cancer (NSCLC) is the most commonly diagnosed cancer type that can be difficult to control with conventional chemotherapeutic and surgical approaches resulting in a poor prognosis. Paclitaxel (PTX) is a commonly used chemotherapeutic drug for NSCLC, which can cause tissue injury in healthy cells and affect the quality of life in patients with cancer. In order to treat NSCLC, alternative medications with minimal or no side effects are highly needed. Ononin is an isoflavone glycoside extracted from Astragali Radix (AR) that has various pharmacological activities. Therefore, this study investigated whether ononin inhibits NSCLC progression and promotes apoptosis synergistically with PTX both in vitro and in vivo. Antitumorigenic properties of ononin were determined by MTT assay, colony formation assay, migratory capacity, and apoptotic marker expression in A549 and HCC827 cells. The combination of ononin with PTX increased the expression of apoptotic markers and ROS generation and inhibited cell proliferation through the PI3K/Akt/mTOR signaling pathways. Furthermore, ononin prevented the translocation of NF-κB from cytosol to the nucleus. Also, we used the xenograft NSCLC mice model to confirm the in vivo antitumorigenic efficacies of ononin by reduction of CD34 and Ki67 expressions. Based on the histological analysis, the cotreatment of PTX and ononin reduced PTX-induced liver and kidney damage. Overall, our findings suggested that the therapeutic index of PTX-based chemotherapy could be improved by reducing toxicity with increasing antitumor capabilities when combined with ononin.