INTERNATIONAL CONGRESS OF
CancerGenetics
Exosomes biogenesis was increased in metformin-treated human ovary cancer cells; possibly to mediate resistance
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Reza Abbasi,1,*
1. Urmia university
- Introduction: Exosome derived from tumor cells contribute to the pathogenesis of cancers. metformin, the most usually used drug for type 2 diabetes, has been frequently investigated for anticancer effects. Here, we examined whether metformin effects metformin signaling in human ovary cancer cells in vitro.
- Methods: Human ovary cancer cells, including A2780 and Skov3 cells, were treated with metformin for either 24-48 h. Cell viability and caspase-3 activity were determined by MTT and colorimetric assays respectively. Oil-red-O staining and in vitro, scratch assays were used to examine cellular toxicity and wound healing rate. after treatment with metformin, exosomes were isolated from cells and quantified by acetylcholinesterase(AChE) assay, Dynamic Light Scattering(DLS), and their markers. Genes related to exosome signaling were analyzed by real-time PCR or Western blotting.
- Results: our results showed that metformin decreased the viability of both cell dose/time dependently(P<0.05). metformin increased the activity of of caspase-3(P<0.05) as well as the number of oil-red-o positive cells in both cell lines. in vitro scratch assay showed that the migration rate o metformin-treated cells was decreased(P<0.05),whereas AChE activity of exosome from metformin-treated cells was increased(P<0.05). concurrent with an increase increase in CD63 protein levels, expression of Alix,CD63,CD81,lam-2,and Rab27b up-regulated in treated in treated cells(P<0.05).
- Conclusion: Results indicated that metformin had a cytotoxic effect on ovary cancer cells and enhanced exosome biogenesis and secretion.
- Keywords: exosome, metformin, ovary cancer, Skov3, CD63
