Proteomic Analysis of the Non-genetic Response to Cisplatin in Lung Cancer Cells.

Background: Drug resistance is the main cause of therapy failure in advanced lung cancer. Although non-genetic mechanisms play important roles in tumor chemoresistance, drug-induced epigenetic reprogramming is still poorly understood.

Materials And Methods: The A549 cell line was used to generate cells with non-genetic resistance to cisplatin (CDDP), namely A549/CDDP cells. Bioorthogonal non-canonical amino acid tagging (BONCAT) and mass spectrometry were used to identify proteins modulated by CDDP in A549 and A549/CDDP cells.

Results: Proteins related to proteostasis, telomere maintenance, cell adhesion, cytoskeletal remodeling, and cell redox homeostasis were found enriched in both cell lines upon CDDP exposure. On the other hand, proteins involved in drug response, metabolic pathways and mRNA processing and splicing were up-regulated by CDDP only in A549/CDDP cells.

Conclusion: Our study revealed proteome dynamics involved in the non-genetic response to CDDP, pointing out potential targets to monitor and overcome epigenetic resistance in lung cancer.