Metabolic response to oncolytic myxoma virus construct in ovarian cancer cell lines as revealed by NMR spectroscopy studies
摘要
Oncolytic viruses have emerged as novel promising therapeutic agents for some hard-to-cure cancers. In the present study, we examined different types of ovarian cancer cell lines to determine the permissiveness of myxoma virus constructs and assessed the metabolic changes associated with viral infection. The Kuramochi, OAW42, and OVP10 cell lines were found to be permissive for the viral constructs, while the OVPA8 line was resistant to this treatment. Nuclear magnetic resonance (NMR) spectra of the cellular extracts and intact cells were acquired using a Bruker Avance III 400 MHz spectrometer. The decreased phosphocholine and succinate, as well as the increased glutamine and uridine nucleotides/uridine diphosphate nucleotide sugars are the common metabolic abnormalities detected in the NMR spectra of aqueous extracts obtained from all virus-sensitive cell lines tested 24 h after infection. The decrease in phosphocholine, increased phosphatidylcholine, and uridine nucleotides/uridine diphosphate nucleotide sugars were also evident in the NMR spectra of intact cells. There was no association between infection and increased lactate levels. Such metabolic changes were not observed for non-permissive OVPA8 cells. We conclude that changes in the metabolome could find use in attempts at ovarian cancer therapy based on these oncolytics, as well as in testing combined approaches exploring such changes.