Inhibitory effect of dexamethasone on residual Lewis lung cancer cells in mice after palliative surgery / 国际肿瘤学杂志

ABSTRACT

Objective To investigate the inhibitory effect of dexamethasone on residual Lewis lung cancer cells in mice after palliative surgery.Methods The model of residual Lewis lung cancer cells in C57BL mice after palliative surgery were established,then accordance with the random number table,18 mice were randomly divided into 3 groups with 6 animals in each groupthe normal saline group,cisplatin group,and dexamethasone group.After operation,the subcutaneous tumor nodules of each mouse were measured on days 4-10 using vernier calipers (accuracy of 0.l mm).The expressions of hypoxia induction factor-1α (HIF-1 α) and mean vascular density (MVD) in the normal saline group,cisplatin group and dexamethasone group were assessed by paraffin immunohistochemical assay.The expressions of HIF-1α,VEGF and PCNA mRNA and protein in the three groups were assessed by real-time quantitative PCR and Western blotting.Results Tumor growth curve showed that the tumor volume in cisplatin group (200.34 ± 20.94) mm3 and in dexamethasone group (436.58 ± 37.94)mm3 were obviously decreased compared with the normal saline group (1 398.81 ± 192.85) mm3,with statistically significant differences (t =-1201.75,P ＜ 0.001;t =-921.52,P ＜ 0.001).As Paraffin immunohistochemical assay showed,in cisplatin group and dexamethasone group,the expressions of HIF-1 α(2.67 ± 0.43,1.67 ± 0.43) and MVD counts (17.01 ± 3.24,9.89 ± 2.25) were decreased significantly compared with the normal saline (4.21 ± 0.35,29.75 ± 5.64),with statistically significant differences (t =-1.55,P＜0.001;t=-1.83,P＜0.001;t=-12.68,P＜0.001;t=-18.35,P＜0.001).The results of real-time quantitative PCR showed that the expressions of HIF-1α (0.56 ±0.11),VEGF (0.61 ±0.18) and PCNA mRNA (0.38 ± 0.07) in dexamethasone group were obviously reduced compared with the normal saline group (1.21 ±0.13,1.13 ± 0.26,1.06 ± 0.08),with statistically significant differences (t =-0.55,P ＜ 0.001;t=-0.62,P＜0.001;t=-0.69,P＜0.001).The expressions of HIF-1α (0.31 ±0.12),VEGF (0.30 ± 0.13) and PCNA mRNA (0.18 ± 0.06) in cisplatin group were also obviously reduced compared with the normal saline group,with statistically significant differences (t =-0.73,P ＜ 0.001;t =-0.76,P ＜ 0.001;t =-0.81,P ＜ 0.001).The results of Western blotting showed that the expressions of HIF-1α (85.98 ± 20.86),VEGF (173.28 ± 30.98) and PCNA protein (228.96 ± 22.97) in dexamethasone group were decreased significantly compared with the normal saline group (198.98 ± 29.89,378.98 ± 28.98,357.98 ± 35.98),with statistically significant differences (t =98.78,P ＜ 0.001;t =85.68,P ＜ 0.001;t =120.86,P ＜ 0.001).The expressions of HIF-1 α (65.78 ± 18.62),VEGF (109.43 ± 19.86) and PCNA protein (176.86 ± 22.76) in cisplatin group were decreased significantly compared with the normal saline group,with statistically significant differences (t =132.86,P ＜ 0.001;t =108.68,P ＜ 0.001;t =154.74,P ＜ 0.001).Conclusion Dexamethasone can effectively inhibit the growth and angiogenesis of the residual Lewis lung carcinoma after palliative surgery in mice,and may also provide a new method of postoperative adjuvant therapy for patients,especially who received palliative surgery.