β-Lapachone, an NQO1 bioactivatable drug, prevents lung tumorigenesis in mice

Lung cancer is one of the most lethal cancers with high incidence worldwide. The prevention of lung cancer is of great significance to reducing the social harm caused by this disease. An in-depth understanding of the molecular changes underlying precancerous lesions is essential for the targeted chemoprevention against lung cancer. Here, we discovered an increased NQO1 level over time within pulmonary premalignant lesions in both the Kras^G12D-driven and nicotine-derived nitrosamine ketone (NNK)-induced mouse models of lung cancer, as well as in Kras^G12D-driven and NNK-induced malignant transformed human bronchial epithelial cells (BEAS-2B and 16HBE). This suggests a potential correlation between the NQO1 expression and lung carcinogenesis. Based on this finding, we utilized β-Lapachone (β-Lap), an NQO1 bioactivatable drug, to suppress lung tumorigenesis. In this study, the efficacy and safety of low-dose β-Lap were demonstrated in preventing lung tumorigenesis in vivo. In conclusion, our study suggests that long-term consumption of low-dose β-Lap could potentially be an effective therapeutic strategy for the prevention of lung premalignant lesions. However, further studies and clinical trials are necessary to validate our findings, determine the safety of long-term β-Lap usage in humans, and promote the use of β-Lap in high-risk populations.