The Modulation of Ferroptosis and Apoptosis in Quinoline Compound-Induced Anti-Human Non-Small Cell Lung Cancer Cells and the Immuotherapy
Description: Lung cancer is one of the most mortality in cancer worldwide results from chemoresistance in late-stage patients. Camptothecin (CPT) is a kind of quinoline which induces cell death and apoptosis through causing the double-strand break of genomic DNA. However, due to the suspension of the clinical trial of CPT, we generated a CPT derivative, DFIQ, against lung cancer. We found that a high dose of DFIQ induced apoptosis by autophagy and ROS production in lung cancer. On the other hand, the dosage lower than IC50 of DFIQ enhanced ferroptosis, a novel programmed cell death regulated by p53 and ROS, which is associated with immunotherapy-mediated cell death. Therefore, we expect that the treatment of a high DFIQ dosage induces cell stress and apoptosis, and the treatment of low dosage DFIQ increases the immunotherapy sensitivity for the lung cancer cells. Based on the results, we will achieve three specific aims in this project. (1) We will investigate the mechanism of DFIQ-induced apoptosis and analyze the anti-cancer potential of DFIQ. (2) We will treat the cell with DFIQ and analyze the cell response to immunotherapy. (3) We will investigate the potential effect of DFIQ treatment on gene regulation by next-generation sequencing and find differentially expressed genes. Further, the modifications of DFIQ structure may induce pharmacological activity. We hope the treatment of DFIQ can be used to increase the efficiency against lung cancer by analyzing the mechanism of DFIQ-induced apoptosis and the relationship between immunotherapy and DFIQ treatment.
Amount: TWD 1,150,000
Funding type: research
Funder scheme: 學術補助
Investigators: 邱建智, 林逸翔, 陳義龍, 陳炳宏
Institution: 高雄醫學大學生物科技學系
Funded outputs count: 7
Funder award ID: MOST109-2313-B037-001
OpenAlex ID: G7867903980