Effect of electronic cigarette aerosols on cisplatin resistance in head and neck cancer cells: a collaborative replication study

Cisplatin chemoresistance is a critical challenge in treating head and neck squamous cell carcinoma (HNSCC). Previous research from Manyanga et al. (2021) suggested that e-cigarette (e-cig) aerosol, including formulations with and without nicotine, might increase cisplatin resistance in oral cancer cells. This multicenter replication study aimed to validate the findings and evaluate the oncologic impacts of e-cigarette use during chemotherapy. This in vitro study utilized standardized and harmonized protocols across 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). Aqueous extracts from 1R6F smoke and e-cig vapor were collected using a smoking and a vaping machine, respectively, 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, DNA repair gene expression related to cisplatin-induced damage, and gene/protein expression of cisplatin transporters, were assessed by MTS, NRU, trypan blue exclusion, qRT-PCR, and Western blot assays, respectively. Contrary 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 cells treated with e-cig aerosols and those exposed to cisplatin alone. Analysis of gene and protein expression revealed occasional variations in the levels of cisplatin transporters and DNA repair mechanisms, but these changes were inconsistent. This study did not fully substantiate previous claims that aerosols generated from e-cigarette, with and without nicotine, increase cisplatin resistance. 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 regarding e-cigarette use during chemotherapy.