Inhibitory effect and mechanism of fluorouracil implants on residual tumor of mouse H22 model following radiofrequency ablation

Abstract

Objective To evaluate the effect and mechanism of fluorouracil implants on residual tumor of mouse H22 model following radiofrequency ablation (RFA). Methods The mouse H22 model was established. The tumors were subjected to RFA under the ablation condition of 55 ℃ for 5 min. Fifty-five mouse H22 models were divided into five groups randomly: control group ( group A); RFA group (group B); combined treatments group using RFA and 2 mg fluorouracil implants (group C), 4 mg flu orouracil implants ( group D) and 6 mg fluorouracil implants ( group E). The change of tumor volumes,and tumor weights were detected two weeks after RFA. The microvessel densities (MVD) of the residual tumor were measured by immunohistochemical staining. The expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) were examined by immunohistochemical staining and Western blotting. Results As compared with group A (2. 51 ± 0. 30) cm3, tumor volumes in group B were statistically increased (3. 10 ±0. 20) cm3, those in group C (1.51 ±0. 20) cm3, group D (0. 72 ± 0. 45) cm3 and group E (0. 36 ± 0. 22) cm3 were gradually decreased ( P ＜ 0. 05 ). As compared with group A ( 1.40 ±0. 25) g, the tumor weights in group B were statistically increased (2.51 ±0. 37) g, but those in group C ( 1.33 ±0. 22 g), group D (0. 80 ±0. 21 ) g and group E (0. 01 ±0. 01 ) g were gradually decreased (P ＜0. 05). The inhibiton rate of tumor growth in groups B, C, D and E was - 79%, 5%,43% and 99% respectively. Immunohistochemical staining indicated that the expression levels of VEGF,PCNA and MVD in group B were significantly higher than those in group A, but those in groups C, D and E were gradually lower than those in group A ( P ＜ 0. 05 ). Western blotting revealed that the protein expression levels of VEGF and PCNA in group B were significantly higher than those in group A, but those of VEGF and PCNA in groups C, D and E were gradually lower than those in group A (P＜0. 05). Conclusion Fluorouracil implants inhibits residual tumor of mouse H22 model following RFA significantly by inhibiting the growth and angiogenesis of residual tumor. Key words: Carcinoma,hepatocellular; Radiofrequency ablation; Residual tumor; Fluorouracil implants