Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Errampalli, R.
The cannabinoid receptor agonist WIN-55,212-2 inhibits proliferation, angiogenesis and invasiveness, and induces apoptosis in small intestine neuroendocrine cancer
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2016. pp. 111
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Ghaffari Tabrizi-Wizsy Nassim
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- Abstract:
- Introduction: Extracts from Cannabis, cannabinoids, have been shown to exhibit anticarcinogenic properties. Cannabinoids inhibit several hallmarks of cancer through various molecular mechanisms. In breast cancer, the anticarcinogenic properties are regulated by Id-1, a helix-loop-helix transcription factor inhibitor. According to a previous study of our group, Id-1 is highly expressed in the small intestine neuroendocrine cancer cell line P-STS. Aims of this study: In this study, we investigated the effect of the synthetic unselective CB1 and CB2 receptor agonist on the small intestine neuroendocrine cancer cell line P-STS. Materials and Methods P-STS cells were treated with the unselective CB1 and CB2 agonist WIN-55,212-2. The effects on proliferation and viability were assessed with the CASY® Cell Counter, WST-1 Assays and Ki67 labelling index. Apoptosis was analysed through Caspase-Glo® 3/7 activation and TUNEL Assays. The in vivo effect on angiogenesis and invasion was observed via CAM Assays. Results and Conclusion: Treatment with WIN-55,212-2 induced a concentration-dependent inhibition of cell proliferation. This effect could be shown in terms of cell growth, cell viability and Ki67 expression and occurred under in vitro as well as under in vivo conditions. Additionally, the susceptibility to WIN-55,212-2 was increased in Id-1 silencing and decreased in Id-1 overexpressing P-STS cells. This indicates that Id-1 plays a protective role against WIN-55,212-2 induced inhibition of cell proliferation. Furthermore, Id-1 was downregulated by treatment with WIN-55,212-2, showing that the effects of WIN-55,212-2 on P-STS cells might be mediated by Id-1. Regarding apoptosis, we found that WIN-55,212-2 induces apoptosis under in vitro conditions, but no effect occurred in vivo. WIN-55,212-2 also decreased solid tumour formation and invasiveness. Angiogenesis was enhanced in vitro and inhibited in vivo.