ADVERTISEMENT
Genes associated with angiogenesis may be regulated by metabolic radiotherapy on cholangiocarcinoma cells
Background
Cholangiocarcinoma (CC) is an aggressive bile duct tumor with a high mortality rate and limited treatment. We evaluated the effect of metabolic radiotherapy with 131I considering the expression of Vascular Endothelial Growth Factor (VEGF) and Hypoxia-Induced Factor (HIF-1a) in CCA cell line.
Methods
Extrahepatic CC (TFK-1) and intrahepatic CC (HuCCT1) cells and cholangiocytes (H69) were cultured and subjected to irradiation with 131 I with doses 1, 20 and 60 Gy after 2 and 48 hours and 12 days. Real-time polymerase chain reaction mRNA expression analysis was performed. Significance level was assumed for P < 0.05.
Results
Underexpression of HIF-1a in HuCCT-1 was observed at 2 and 48 hours after irradiation with 1 Gy (0.70 and 0.51), 20 Gy (0.65 and 0.66) and 60 Gy (0.59 and 0.91; P=0.001). In TFK-1, there was HIF-1a underexpression within 2 hours at the dose of 60 Gy (0.08) compared to 1 Gy (1.63) and 20 Gy (1.88; P=0.004). In HuCCT-1, underexpression of VEGF at the three doses at 2 hours and 12 days (1 Gy=0.26 and 0.37; 20 Gy=0.53 and 0.61; 60 Gy=0.41 and 0.23, respectively) compared to 48 hours (1 Gy=0.56; 20 Gy=0.99; 60 Gy=0.93; P=0.01 and P=0.03). In TFK-1, underexpression of VEGF was highlighted at a dose of 20 Gy in 48 hours (0.53) and 12 days (0.23) compared to 2 hours (19.42; P < 0.0001).
Conclusions
Radiotherapy with 131I at different doses and exposure time is associated with underexpression of HIF and VEGF in intra- and extra-hepatic CCA cells.
Legal entity responsible for the study
The authors.
Funding
National Council for Scientific and Technological Development (CNPq).
Disclosures
All authors have declared no conflicts of interest.
