摘要
目的:探讨联合抑制缺氧诱导因子1α(HIF-1α)和信号转导子和转录激活子3(STAT3)对裸鼠人喉鳞状细胞癌移植瘤化疗增敏的作用。方法:将制备的喉癌移植瘤裸鼠随机分为空白对照组(A组)、顺铂化疗组(B组)、顺铂化疗联合AG490组(C组)、顺铂化疗联合HIF-1α^(-/-)组(D组)、顺铂化疗联合AG490加HIF-1α^(-/-)组(E组)和HIF-1α^(-/-)组(F组)。给予腹腔注射顺铂3 mg/kg连续3d,然后间隔给予顺铂和10mg/kg AG490连续12d。应用免疫组织化学法检测Ki67和HIF-1α表达。应用Western blot法检测p-STAT3表达。结果:C组、D组与B组比较HIF-1α表达均有显著差异(t值分别为2.782、3.873,均P<0.05);E组与C组、D组比较HIF-1α表达均有显著差异(t值分别为6.140、3.667,均P≤0.01)。C组与B组比较p-STAT3表达明显降低(t=17.840,P<0.01);D组与B组比较p-STAT3表达无明显差异(t=0.038,P>0.05);E组与C组、D组比较p-STAT3表达明显降低(均P<0.01)。E组与B组比较抑瘤率有显著差异(t=5.509,P<0.01);E组与C组、D组比较抑瘤率均有显著差异(t值分别为3.422、2.718,均P<0.05)。E组与B组、D组比较Ki67指数有显著差异(t值分别为8.307、4.524,均P<0.01);E组与C组比较Ki67指数有显著差异(t=3.736,P<0.05)。结论:联合抑制HIF-1α表达和STAT3通路对于头颈鳞状细胞癌的增殖抑制作用明显较单独抑制一种通路强。
Objective： To investigate the effects of combined inhibition of signal transducer and activator of transcription 3（STAT3） and hypoxia-inducible factor-lα （HIF-1α）in the enhancement of chemosensitivity of the model of human laryngeal squamous eacinoma in nude mice. Method： Model nude mice were divided into six groups randomly： control group（A）, cisplatin group（B）, cisplatin and AG490 group（C）, cisplatin and HIF-la-/- group （D）, cisplatin combined AG490 and HIF-la-/- group（E）, HIF-la-/- group（F） （only in calculating tumor inhibi- tion rate）. 3mg/kg cisplatin was administered by peritoneal injection for 3 days. Then cisplatin and 10 mg/kg AG490 were administered every other day for 12 days. The expression of Ki67 and HIF-1α was detected by immu- nocytochemical method. Western blot was used to detect the expression of p-STAT3. Result： The expression of HIF-la in group C and group D were lower than that in group B, and there were significant difference respectively （tl=2. 782, t2 =3. 873,P〈0.05） ;The expression of HIF-la in group E was lower than that in group C and group D respectively, and there were significant difference respectively （tl = 6. 140, t2 = 3. 667, P≤0.01）. The expres- sion level of p-STAT3 in group C was markedly lower compared with that in group B, and there were significant difference between them （t= 17. 840, P〈0.01）;There were no difference between the expression level of p- STAT3 in group D and that in group B（t= 0. 038,P〉0.05） ;The expression level of p-STAT3 in group E was sig- nificantly lower compared with that in group C and group D respectively （P〈 0.01）. Tumor inhibition rate of group E was higher than that in group B, group C , as well as group D respectively and there were significant difference respectively（t1=5. 509,P〈0.01; t2 =3. 422,P〈0.05 ; t3 =2. 718,P〈0.05 ）. Ki67 index of group E was lower than that in group B, group C as well as group D respectively and there were significant difference re- spectively（tl =8. 307,P〈0.01; t2 =3. 736,P〈0.05 ; ta =4. 524,P〈0.01）. Conclusion： Combined inhibition of STAT3 and HIF-la could enhance cherno-sensitivity in the model of human laryngeal squamous cacinoma in nude mice.
出处
《临床耳鼻咽喉头颈外科杂志》
CAS
北大核心
2016年第4期314-318,共5页
Journal of Clinical Otorhinolaryngology Head And Neck Surgery
基金
河北省自然科学基金资助项目(No:H2012505005)
