Chemotherapeutic Sensitization of Leptomycin B Resistant Lung Cancer Cells by Pretreatment with Doxorubicin

The development of novel targeted therapies has become an important research focus for lung cancer treatment. Our previous study has shown leptomycin B (LMB) significantly inhibited proliferation of lung cancer cells; however, p53 wild type lung cancer cells were resistant to LMB. Therefore, the objective of this study was to develop and evaluate a novel therapeutic strategy to sensitize LMB-resistant lung cancer cells by combining LMB and doxorubicin (DOX). Among the different treatment regimens, pretreatment with DOX (pre-DOX) and subsequent treatment with LMB to A549 cells significantly decreased the 50% inhibitory concentration (IC50) as compared to that of LMB alone (4.4 nM vs. 10.6 nM, PPP新型靶向治疗药物的开发已成为肺癌治疗领域的重要研究热点。本团队前期研究表明，亮霉素B（leptomycin B, LMB）可显著抑制肺癌细胞增殖，但p53野生型肺癌细胞对亮霉素B存在耐药性。因此，本研究旨在开发并评估一种全新治疗策略，通过联合使用亮霉素B与多柔比星（doxorubicin, DOX）来增敏耐亮霉素B的肺癌细胞。在多种给药方案中，对A549细胞先施以多柔比星预处理（pre-DOX）后再给予亮霉素B治疗，相较单独使用亮霉素B，其半数抑制浓度（50% inhibitory concentration, IC50）显著降低（4.4 nM vs. 10.6 nM，PP）