Molecular and biological effects of Cisplatin in Drosophila

Cisplatin is widely used in cancer treatment and is one of the best cytostatic agents available for antitumor therapy. Drosophila melanogaster has one of the best annotated genomes and one of the best characterized sets of transposable elements (TE) sequences. This model organism is useful for analyzing the mode of action of several compounds in vivo and evaluating the behavioral consequences of treatments. The aim of our study was to increase the knowledge about the effects of Cisplatin in Drosophila by joining RNA-seq and biological assays. RNA-seq was followed by analyses of differential expression of genes (DEGs) and TEs (DETEs), and of pathways and ontology terms. DETEs were confirmed by qPCR. Cisplatin was evaluated at 50 and 100 μg/mL in Drosophila culture medium for 24 h. The fly locomotor assay, survival analysis, oviposition and development were used as biological assays. Cisplatin induced DEGs in a dose-dependent fashion, and four TEs were up-regulated. Most DEGs are related to DNA damage and detoxification processes. Cisplatin increases Drosophila locomotor activity and interrupts development. Genes and processes related to the assays were also identified. This is the first study to evaluate the effects of Cisplatin in flies using RNA-seq. Gene alteration was almost limited to drug metabolism and DNA damage, and the drug did not vastly affect Drosophila on the molecular level. Contrary to the hypothesis that stress dramatically alters TEs mobilization, only four TEs were up-regulated. Our study, together with previous knowledge, asserts Drosophila as a valuable organism in the study of chemotherapy drugs.