| AVS 64th International Symposium & Exhibition | |
| Plasma Processing for Biomedical Applications Focus Topic | Tuesday Sessions |
| Session PB+BI+PS-TuM |
| Session: | Plasma Medicine |
| Presenter: | Deborah O'Connell, University of York, UK |
| Authors: | J. Packer, University of York, UK A.M. Hirst, University of York, UK F.M. Frame, University of York, UK D. O'Connell, University of York, UK N.J. Maitland, University of York, UK |
| Correspondent: | Click to Email |
Low-temperature plasma (LTP) treatment of cancer cells have been explored for a variety of malignancies. These plasmas, operated at atmospheric pressure and close to room temperature, are efficient sources of reactive oxygen and nitrogen species (RONS), electric fields and photons, and can induce a variety of biological responses. There is an increasing clinical move towards focal therapy for more conservative management of prostate cancer, with reduced levels of common side effects such as incontinence and impotence compared with radical treatments, and promising outcomes. Low-temperature plasmas may offer such potential.
A dielectric barrier discharge jet, created within a glass tube surrounded by two electrodes (~ 6 kV applied sinusoidal voltage), with a helium plus 0.3% oxygen gas flow is used for these investigations. We have employed both purified tumour cells freshly extracted from prostate cancer patients, and matching, non-tumour cells from a distant region of the same prostate. Freshly isolated primary tumour cells acts as a near patient model, which has recently confirmed differences in pharmacological susceptibility as compared with 30 year old established cell lines.
Treatment of primary prostate epithelial cells with LTP resulted in sigificant cell death in both normal and cancer cells; and no significant selectivity observed, as commonly reported. In addition, most cells appeared to die via a necrotic mechanism, rather than apoptosis, maybe as a result of the mitochondrial toxicities of the LTP-activated reactive oxygen species (ROS). However, some autophagy was also detected, which has been shown to act as a salvage pathway for sub-lethally damaged cells.
To determine which of the multiple plasma activated bio-reactive species are responsible for the cytotoxicity, we have explored immediate and longer-term effects on gene expression, with a particular focus on oxidative responses, in multiple patient samples. Comparative studies in the established cell lines indicated a delayed and different response, highlighting that cell lines don’t always reflect the response of primary cells. Expression of 84 genes (mRNA by RT2 arrays from Qiagen) was assessed at multiple time points, after a 3 minute LTP treatment, and candidate genes/response pathways were identified. Immunofluorescence and western blotting were used to verify changes in protein expression. The response varied according to the clinical grade of the tumour (including a remarkable downregulation of 18 factors only seen in the highest grade tumours). All epithelial cells showed a stimulation of transcription factor-driven anti-oxidative response, as a potential resistance mechanism.