Loratidine is associated with improved prognosis and exerts antineoplastic effects via apoptotic and pyroptotic crosstalk in lung cancer

作者：Liu, Xiwen; Zhong, Ran; Huang, Jiaxing; Chen, Zisheng; Xu, Haoxiang; Lin, Lixuan; Cai, Qi; He, Miao; Lao, Shen; Deng, Hongsheng; Li, Caichen; Li, Jianfu; Zheng, Yongmei; Liu, Xiaoyan; Zeng, Riqi; He, Jianxing; Liang, Wenhua

来源：JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2024, 43(1): 5.

DOI：10.1186/s13046-023-02914-8

• Lung cancer
• Loratadine
• Apoptosis
• Pyroptosis
• Caspase8

BackgroundTumor-associated inflammation suggests that anti-inflammatory medication could be beneficial in cancer therapy. Loratadine, an antihistamine, has demonstrated improved survival in certain cancers. However, the anticancer mechanisms of loratadine in lung cancer remain unclear.ObjectiveThis study investigates the anticancer mechanisms of loratadine in lung cancer.MethodsA retrospective cohort of 4,522 lung cancer patients from 2006 to 2018 was analyzed to identify noncancer drug exposures associated with prognosis. Cellular experiments, animal models, and RNA-seq data analysis were employed to validate the findings and explore the antitumor effects of loratadine.ResultsThis retrospective study revealed a positive association between loratadine administration and ameliorated survival outcomes in lung cancer patients, exhibiting dose dependency. Rigorous in vitro and in vivo assays demonstrated that apoptosis induction and epithelial-mesenchymal transition (EMT) reduction were stimulated by moderate loratadine concentrations, whereas pyroptosis was triggered by elevated dosages. Intriguingly, loratadine was found to augment PPAR gamma levels, which acted as a gasdermin D transcription promoter and caspase-8 activation enhancer. Consequently, loratadine might incite a sophisticated interplay between apoptosis and pyroptosis, facilitated by the pivotal role of caspase-8.ConclusionLoratadine use is linked to enhanced survival in lung cancer patients, potentially due to its role in modulating the interplay between apoptosis and pyroptosis via caspase-8.

• 单位
  广东省人民医院; 南方医科大学; 广州医学院; 1; 广州中医药大学; 6