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Research Highlight | February 15, 2018

Ultrasound-stimulated microbubbles enhance radiation effect on prostate cancer cells

What if there was a way to make cancer cells more susceptible to radiation therapy without damaging healthy cells? New findings from Toronto researchers have shown ultrasound- stimulated microbubbles is a novel type of treatment that may achieve just that.   

Dr. Gregory Czarnota’s cancer imaging team at Sunnybrook Health Sciences Centre conducted the first study investigating the UGT8 signalling pathway in prostate cancer and found it plays an important role in how tumours respond to ultrasound-stimulated microbubble-enhanced radiation treatment.

The findings, published in PLOS One (July 17), showed that the down-regulation of UDP glycosyltransferase 8 (UGT8) resulted in more cell death signalling and a greater enhancement of radiation effect when vascular disruption takes place by using ultrasound-stimulated microbubbles. Microbubbles are 1 to 8 μm diameter bubbles comprised of a gas core and stabilized by a protein shell or thin lipid.

The team carried out experiments both in vitro in cells and tumours in vivo to examine the role of UGT8 in responses to prostate cancer tumours exposed to the ultrasound-stimulated microbubble radiation therapy. The genetically modified prostate cancer cells were treated with either radiation or the ultrasound microbubbles treatment, or a combination of both. The results showed that in cells where UGT8 was down-regulated more cancer cells were destroyed compared to when UGT8 was up-regulated or not regulated at all.

Further, xenograft tumours generated from stably transfected prostate cancer cells were also treated with either radiation alone or the ultrasound microbubbles treatment, or in combination. Again, there was more cell death in cells with down-regulated UGT8 compared to control tumours and up-regulated UGT8. 

The study suggests that down-regulating UGT8 leads to increased ceramide levels (a favoured biochemical mechanism leading to endothelial cell death), which creates more cell death signalling. This in turn allows the effects of radiation to be enhanced when the ultrasound-stimulated microbubbles create vascular disruption. Tumour cell death is most efficient when endothelial cell death results in microvascular deterioration. Using ultra-sound activated microbubbles in combination with a specific gene therapy could be a novel, cutting-edge form of cancer therapy that may benefit patients in the future.

Study: Microbubble-based enhancement of radiation effect: Role of cell membrane ceramide metabolism

Authors: Azza Al-Mahrouki, Anoja Giles, Amr Hashim, Hyunjung Christina Kim, Ahmad El-Falou, Dean Rowe-Magnus, Golnaz Farhat, Gregory J Czarnota

Funding: This study was funded in part by a Terry Fox New Frontiers Project Program grant in ultrasound and MRI for cancer therapy.