Multi-Center "Replica Study" Challenges the Impact of Electronic Cigarette Aerosols on Cisplatin Resistance in Head and Neck Cancer Cells

BackgroundCisplatin chemoresistance is a critical challenge in the treatment of head and neck squamous cell carcinoma (HNSCC). Since previous research has suggested that nicotine and e-cigarette (e-cig) aerosol might increase cisplatin resistance in oral cancer cells, this multicenter replication study aimed to replicate the work by Manyanga et al. (2021) and evaluate the oncologic implications of e-cigarette exposure during chemotherapy. MethodsThis in vitro study involved standardized and harmonized protocols in international laboratories to examine the effects of cigarette smoke (1R6F) and e-cig aerosols with different concentrations of nicotine (0, 12, and 20 mg/ml nicotine) on cisplatin sensitivity in HNSCC cell lines (SCC-25, FaDu, and UM-SCC-1). Aerosols from 1R6F smoke and e-cig vapor were collected using a smoking and vaping machine, following ISO20778:2018 and ISO20768:2018 puffing regimes. The smoke and vapor were collected in PBS and diluted to 10 puffs/5L for HNSCC cell treatment. Chemosensitivity, clonogenicity, expression of gene for repair of cisplatin-induced DNA damage and gene and protein expression of cisplatin transporters were assessed by MTS, NRU, trypan blue, PCR, and Western blot assays, respectively. ResultsContrary to previous findings, exposure to e-cig aerosols did not significantly modulate cisplatin sensitivity in all cell lines. IC50 values, cytotoxicity assays, and clonogenic survival rates remained similar between e-cig treatments and cisplatin alone. Analysis of gene and protein expression revealed sporadic changes in the levels of transporters and repairs of cisplatin-induced DNA damage. ConclusionsThis study did not fully substantiate previous claims of increased cisplatin resistance due to e-cigarette aerosols and nicotine. The variability in gene and protein expression among different cell lines underscores the need for cautious interpretation and further investigation of the role of e-cigarette components in cancer treatment. These findings provide a critical perspective for shaping public health policies and clinical practices related to e-cigarette use during chemotherapy.