Background/Aim: Cisplatin combined with pemetrexed disodium heptahydrate (pemetrexed) is considered the standard treatment for patients with advanced, non-squamous, non-small-cell lung cancer. However, its growth-inhibitory effects on KRAS-dependent lung cancer as monotherapy and combination therapy are not well understood. The aim of this study was to compare the effects of cisplatin and pemetrexed on A549 cells as mono- and combination therapies and elucidate the underlying mechanisms. Materials and Methods: For in vitro studies, A549 cells were exposed to cisplatin with/without pemetrexed for 72 h. The results were then evaluated by cell viability, apoptosis, reactive oxygen species, terminal deoxynucleotidyl transferase dUTP nick-end labeling, and western blotting assays. Results: Our results revealed that cisplatin monotherapy was most cytotoxic to A549 cells, while cisplatin plus pemetrexed combination had an intermediate effect, and pemetrexed monotherapy induced a minimal cytotoxic effect on A549 cells. This effect was evidenced by cell viability results, inhibition of KRAS proto-oncogene, GTPase (KRAS)/Raf proto-oncogene, serine/ threonine kinase/mitogen-activated protein kinase kinase/ extracellular signal-regulated kinase pathways and apoptosis induction triggered by reactive oxygen species-mediated DNA damage. The immunoblotting result of conversion of microtubule-associated protein 1 light chain 3 alpha (LC3)I to -II indicated that the greatest inducer of autophagy was combined treatment with cisplatin plus pemetrexed, while.
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Mohiuddin, M., & Kasahara, K. (2021). Cisplatin and pemetrexed have distinctive growth-inhibitory effects in monotherapy and combination therapy on KRAS-dependent A549 lung cancer cells. Cancer Genomics and Proteomics, 18(4), 579–590. https://doi.org/10.21873/CGP.20282