Abstract 7599: Evaluate the treatment efficacy of magnolol combined with cisplatin in non-small cell lung cancer
Authors: Lu Rong-Er , Chen Bo-Xun , Hsu Fei-Ting , Chiang I-Tsang 
Published: March 2024

Abstract
Lung cancer is one of the five most common cancers in the world. Statistics indicate that approximately 80% to 90% of lung cancer cases fall under the classification of non-small cell lung cancer (NSCLC). For several decades, non-small cell lung cancer (NSCLC) has often been treated with chemotherapy drugs. However, lung cancer has high incidence and recurrence rates, mainly due to drug resistance and side effects during chemotherapy and radiotherapy. This is the hinder problem in the treatment of NSCLC, which highlight the necessity of developing new drugs or new treatments for NSCLC. Cisplatin is a chemotherapy drug that can treat about 50% of solid tumors, but the cisplatin-induced cytoprotective autophagy is the resistance to clinical treatment. It is urgent to elucidate the underlying molecular mechanisms regulating cisplatin resistance to improve its therapeutic value in lung cancer. Magnolol is a phenolic component isolated from the roots and bark of Magnolia officinalis and is used in traditional Chinese medicine. With a wide range of pharmacological activities, various studies have focused on the anti-cancer properties of magnolol in recent years. The effect of the drug is to keep cells in the G2/M phase, induce mitochondrial dysfunction and ROS production, affect the supply of cellular energy, and then lead to cell apoptosis. In this study, we investigated the ability of magnolol enhance cisplatin-induced cytotoxicity, showing dose dependence in NSCLC cell by MTT assay. We utilized the immunofluorescence staining and western blotting assay to confirm the downgrade expression of LC3B and the upregulate expression of p62 that define magnolol is able to suppress cisplatin-induced cytoprotective autophagy in NSCLC. We also detected the extrinsic/intrinsic apoptosis induction ability of magnolol combined with cisplatin in NSCLC. In the result, the cisplatin combined with magnolol have more significantly triggered the loss of mitochondrial membrane potential, and activate more protein cleaved caspase-3, -8 and -9 than monotherapy. We also used western blotting assay to confirm the expression of apoptosis inhibitory protein Bcl-2 and pro-apoptotic protein Bax to measure the degree of apoptosis. The migration and invasion effects of magnolol and cisplatin were identified by transwell invasion and wound healing on NSCLC. The magnolol combined with cisplatin extended the mouse survival rate and can inhibit tumor progression. These results suggest that combinational therapy of cisplatin and magnolol could be a promising treatment strategy for NSCLC. The potential regulation of magnolol on NSCLC is associated with triggering cisplatin-induced apoptosis and diminishing cisplatin-induce cytoprotective autophagy.
Citation Format: Rong-Er Lu, Bo-Xun Chen, Fei-Ting Hsu, I-Tsang Chiang. Evaluate the treatment efficacy of magnolol combined with cisplatin in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7599.