Abstract 1095: Establishment and characterization of a topotecan resistant lung cancer NCI H460/TPT10 cell line and a tumor xenograft model

Abstract

Abstract While topotecan (TPT) is a chemotherapeutic drug in treating lung cancer, the development of TPT resistance in tumors reserves as a major obstacle to chemotherapeutic success. Therefore, a better understanding of the mechanisms of TPT resistance is critical. In this study, the first topotecan-resistant human non-small cell lung cancer (NSCLC) cell line, termed NCI-H460/TPT10, was established from the parental NCI-H460 cell line. NCI-H460/TPT10 cells exhibited a 394.7-fold resistance to TPT, and cross-resistance to SN-38, mitoxantrone, and doxorubicin, compared to parental NCI-H460 cells. Overexpression of ABCG2 localized on the cell membrane, but not ABCB1 or ABCC1, was found in NCI-H460/TPT10 cells, indicating that ABCG2 was likely to be involved in TPT-resistance. This was confirmed by the abolishment of drug resistance in NCI-H460/TPT10 cells after ABCG2 knockout. Moreover, the involvement of functional ABCG2 as a drug efflux pump conferring multidrug resistance (MDR) was indicated by low intracellular accumulation of TPT in NCI-H460/TPT10 cells, and the reversal effects by ABCG2 inhibitor Ko143 and cabozantinib. The NCI-H460/TPT10 and its parental cell line were further used to establish in vivo tumor xenograft mouse models, which verified their capability to serve as clinically relevant models for drug screening and the development of targeted strategies to overcome ABCG2-mediated MDR in NSCLC. Citation Format: Qiu-Xu Teng, Zi-Ning Lei, Wei Zhang, Ying-Fang Fan, Jing-Quan Wang, Chao-Yun Cai, Dong-Hua Yang, John Wurpel, Zhe-Sheng Chen. Establishment and characterization of a topotecan resistant lung cancer NCI H460/TPT10 cell line and a tumor xenograft model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1095.