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.
ABSTRACT
Objective To investigate the effect of different subtypes of fractionated doses on multidrug resistance in ovarian cancer cells.Methods The human ovarian cancer cell lines SKOV3 and its drug-resistant subtype SKVCR were divided into four groups i.e., sham-irradiated, single dose (10 Gy),fractionated dose (2 Gy × 5 ) and multi-fractionated dose (1 Gy × 2 × 5).Cell sensitivity to vincristine(VCR),etoposide ( VP-16),pirarubicin (THP) and cisplatin (DDP) was measured by MTT assay.Western blot was applied to detect the expression of P-gp after irradiation.Results The doubling time of SKVCR was about 1.8-fold of that of SKOV3 cells.P-gp was expressed in SKVCR but not in SKOV3.IC50 values of SKVCR were higher than those of SKOV3.To SKOV3 cells,single dose irradiation decreased cell sensitivity to THP and DDP and fractionated irradiation decreased cell sensitivity to VCR,THP and VP-16.Multi-fractionated irradiation decreased cell sensitivity to VP-16.In SKVCR cells,all these irradiation treatments increased cell sensitivity to VCR and VP-16 but not to DDP.In addition,single and fractionated irradiation decreased P-gp expression in SKVCR cells.Conclusions Single,fractionated and multi-fractionated radiation induced chemotherapy resistance in SKOV3 cells,while reversed drug resistance to VCR and VP-16 in SKVCR cells.