Effects of fractionated irradiation on the invasion and metastasis of residual HepG2 cells / 中华放射医学与防护杂志

ABSTRACT

Objective To investigate the changes of invasion and migration potential of residual hepatocarcinoma cells after fractionated X-ray irradiation and its underlying mechanism.Methods HepG2 cells were exposed to X-rays (2 Gy × 10) and recovered for 30 days after irradiation to generate residual cells.The changes of cellular invasion and migration potential were detected in the residual and its control cells using a Transwell assay.The expressions of epithelial-mesenchymal transition(EMT)-related proteins of N-cadherin and Snail were detected by Western blot.HepG2 subcutaneous tumor models were established using nude mice that were divided into control and radiation group.In radiation group,the tumors were locally irradiated with a dose of 2 Gy per fraction daily,5 days per week for 2 weeks until the cumulative dose reached to 20 Gy.The growth of the tumor was observed,and on the day 39 after cell implantation (i.e.day 14 after radiation),the liver metastasis and the expression of N-cadherin in tumor with or without radiation were detected.Results The invasions and migrations of the residual cells and xenograft tumor were significantly enhanced in comparison with the control group (t =5.126,7.714,P ＜0.05).The expressions of N-cadherin and Snail in the radiation group were significantly higher than that in the control group (t =7.509,7.184,P＜0.05).In the HepG2 subcutaneous tumor model,the weight and volume of tumor in nude mice of the radiation group was significantly smaller than that in the control group (t =2.396,3.170,P ＜0.05),and the number of liver metastases in nude mice and the expression of N-cadherin in tumor were significantly higher than those in the control group (t =2.994,5.695,P ＜0.05).Conclusions Fractionated irradiation enhances the abilities of invasion and migration by inducing EMT in hepatocarcinoma cells,which provides new insights of the recurrence and metastasis of hepatocarcinoma after radiotherapy.