Abstract 1571: The feasibility and pharmacological mechanism of cucurbitacin E for the treatment of EGFR-TKI-primary resistant NSCLC

Abstract

Abstract Lung cancer ranks the leading cause of cancer death, with an estimated 1.8 million deaths according to the latest global cancer statistics. In the United States, there will be an estimated 236,740 new cases diagnosed, and 130,180 people will die from lung cancer in 2022. In non-small-cell lung cancer (NSCLC) patients, targeted therapies are available for patients with EGFR exon 19 deletion and L858R mutations. However, tumors harboring wild-type EGFR or Kras mutation are not eligible for targeted therapies. Therefore, the development of new drugs to treat primary resistant NSCLC remains urgent needs. Cucurbitacin E (CuE) is a tetracyclic triterpenoid compound extracted from the family of Cucurbitaceae. The data showed that CuE exhibits a significant antiproliferative effect with a GI50 value of 0.03±0.01 μM. Cell cycle analysis revealed that CuE induces G2/M arrest and down-regulates cell cycle regulatory proteins in A549 cells. CuE treatment further increased the expression of cleaved caspase-3/8/9/PARP, and altered the expression of DNA-damaged-related biomarkers. Meanwhile, protein levels of LC3BII and p62, and ROS production were upregulated by CuE. Pharmacological Inhibition of ATM reversed the effects of CuE on autophagy-related proteins. In summary, CuE is a potential drug for the treatment of primary resistant NSCLC. Citation Format: Chun-Han Chen. The feasibility and pharmacological mechanism of cucurbitacin E for the treatment of EGFR-TKI-primary resistant NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1571.