白蔹素灌胃治疗及联合放射治疗的鼻咽癌模型小鼠肿瘤生长情况观察

Tumor growth of nasopharyngeal carcinoma model mice treated by gastric administration of Baifusu and radiotherapy

目的观察白蔹素灌胃治疗及联合放射治疗(以下简称放疗)的鼻咽癌模型小鼠肿瘤生长情况,并探讨白蔹素的可能作用机制.结果雄性清洁级BALB/c(nu/nu)裸小鼠50只,接种CNE-2细胞制备鼻咽癌小鼠模型,造模成功48只.将48只小鼠随机均分为模型对照组、白蔹素组、放疗组、白蔹素+放疗组,每组12只.模型对照组每天生理盐水灌胃;白蔹素组每天50 mg/kg白蔹素灌胃;白蔹素+放疗组每天50 mg/kg白蔹素灌胃后,进行肿瘤局部单次8 Gy照射;放疗组每天灌胃生理盐水,然后给予肿瘤局部单次8 Gy照射,各组均干预21 d.开始干预后每7天测量一次肿瘤直径,干预28天取各组小鼠处死后测量肿瘤直径,测算抑瘤率,免疫组化法检测各组肿瘤组织血管内皮生长因子(VEGF)、增殖细胞核抗原(PCNA).结果干预14 d时,与模型对照组比较,白蔹素组、白蔹素+放疗组肿瘤直径减小(P均<0.05);干预28 d时,与模型对照组比较,放疗组、白蔹素组、白蔹素+放疗组肿瘤直径减小(P均<0.05);干预28 d时,放疗组、白蔹素组、白蔹素+放疗组肿瘤直径两两比较,P均<0.05.干预28 d时,放疗组、白蔹素组、白蔹素+放疗组抑瘤率分别为34.27%±5.13%、27.93%±4.75%、48.60%±6.20%,与放疗组、白蔹素组比较,白蔹素+放疗组抑瘤率高(P均<0.05).模型对照组、放疗组、白蔹素组、白蔹素+放疗组肿瘤组织VEGF表达量分别为0.041±0.004、0.017±0.004、0.015±0.002和0.003±0.002,肿瘤组织PCNA增殖指数分别为31.02%±2.45%、17.04%±2.55%、10.36%±3.15%和9.15%±1.72%;与模型对照组比较,放疗组、白蔹素组、白蔹素+放疗组肿瘤组织VEGF表达量、PCNA增殖指数降低(P均<0.05),放疗组、白蔹素组、白蔹素+放疗组肿瘤组织VEGF表达量、PCNA增殖指数两两比较,P均<0.05.结论白蔹素可抑制鼻咽癌小鼠的肿瘤生长,白蔹素灌胃治疗及联合放疗抑制鼻咽癌小鼠肿瘤生长的效果优于白蔹素灌胃.白蔹素可能是通过抑制肿瘤组织PCNA、VEGF的表达来发挥抑瘤作用的.

Objective To observe the effect of Baifusu intragastric administration combined with radiotherapy(hereinafter referred to as radiotherapy)on the growth of nasopharyngeal carcinoma(NPC)in mice,and to explore the mechanism of Baifusu.Methods Fifty male clean BALB/c(nu/nu)nude mice were inoculated with CNE-2 cells to prepare NPC models.Forty-eight of them were successfully established.The 48 mice were randomly divided into the model control group,Baifusu group,radiotherapy group,Baifusu+radiotherapy group,with 12 mice in each group.The mice in the model control group were given normal saline daily,the Baifusu group was given 50 mg/kg Baifusu daily,the Baifusu+radiotherapy group was given a single dose of 8 Gy irradiation after 50 mg,/kg Baifusu daily,and the radiotherapy group was given normal saline daily,then a single dose of 8 Gy irradiation for 21 days.Tumor volume was measured every 7 days after intervention.Tumor volume was measured after 28 days of intervention.Tumor inhibition rate was calculated.Vascular endothelial growth factor(VEGF)and proliferating cell nuclear antigen(PCNA)were detected by immunohistochemistry.Results Compared with the model control group,the diameter of tumors in the Baifusu group and Baifusu+radiotherapy group decreased at 14 days after intervention(P<0.05);compared with the model control group,the diameter of tumors in the radiotherapy group,Baifusu group and Baifusu+radiotherapy group decreased at 28 days after intervention(P<0.05/;at 28 days after intervention,the diameter of tumors in the radiotherapy group,Baifusu group,Baifusu+radiotherapy group decreased(P<0.05);at 28 days after intervention,the diameter of tumors in the radiotherapy group,Baifusu group,Baifusu+radiotherapy group decreased.At 28 days after intervention,the inhibition rate of Baifusu+radiotherapy group was 48.60%±6.20%,which was higher than those in the the radiotherapy group and Baifusu group(P<0.05).Compared with the model control group,the VEGF expression and PCNA proliferative index in the tumor tissues of the radiotherapy group,the Baifusu group,the Baifusu+radiotherapy group decreased(all P<0.05),and significant difference was found in the VEGF expression and PCNA proliferative index between the radiotherapy group,the Baifusu group and the Baifusu+radiotherapy group(all P<0.05).The VEGF expression and PCNA proliferation index were the highest in the model group(0.041±0.004 and 31.02%±2.45%,respectively),and the lowest in the Baifusu+radiotherapy group(0.003±0.002 and 9.15%±1.72%,respectively).Conclusion Baifusu can inhibit the NPC growth in mice by inhibiting the expression of PCNA and VEGF in tumor tissues,and the combined treatment of Baifusu and radiotherapy can inhibit the growth of nasopharyngeal carcinoma in mice better than Baifusu or radiotherapy alone.