TLR9对胰腺癌裸鼠增殖生长及化疗耐药性的研究  

Research on influence of TLR9 on pancreatic cancer nude mouse model growth and resistance to chemotherapy

作　　者：刘宇[1] 雷泽华[1] 杜波[1] 王志旭[1] 高峰畏 王清[1] 张建新[2] 

机构地区：[1]四川省乐山市人民医院普外科,614000 [2]江苏大学附属医院,江苏镇江212001

出　　处：《重庆医学》2017年第16期2167-2169,2173,共4页Chongqing medicine

基　　金：国家自然科学基金资助项目(81070287)

摘　　要：目的观察TLR9在不同的活化状态下对人胰腺癌裸鼠移植瘤生长及药物抗性的影响。方法建立人胰腺癌PANC-1细胞裸鼠移植肿瘤模型,并随机分为6组:无菌生理盐水组、TLR9激动剂、TLR9抑制剂组、吉西它滨组、TLR9抑制剂+吉西它滨组、TLR9激动剂+吉西它滨组进行实验。游标卡尺记录肿瘤体积大小及生长情况,采用免疫组化方法检测肿瘤TLR9受体表达情况,核磁共振成像(MRI)观察肿瘤生长、转移及周围组织侵犯情况。结果吉西他滨组、TLR9激动剂+吉西它滨组、TLR9抑制剂+吉西它滨组肿瘤摘除后体积及生长速度明显小于其他组(P<0.05),TLR9激动剂+吉西它滨组生长速度及肿瘤摘除后体积明显大于TLR9抑制剂+吉西它滨组及吉西他滨组(P<0.05),TLR9抑制剂+吉西它滨组与吉西他滨组比较,差异有统计学意义(P<0.05),TLR9激动剂组、TLR9抑制剂组及生理盐水组差异无统计学意义(P>0.05)。种植后7周小鼠在MRI下观察,瘤成椭圆形,境界清楚,周围组织未见明显转移及对周围组织的侵犯;检测肿瘤组织中并鉴定表面明确有TLR9的表达。结论胰腺癌裸鼠移植瘤中确有TLR9的阳性表达,TLR9的激活可以明显降低胰腺癌对吉西他滨化疗的敏感性,增加肿瘤的耐药性,相反促进肿瘤生长。Objective To observe the effects of TLR9 on the nude mouse transplanted tumor growth of human pancreatic cancer and its drug resistance. Methods The nude mouse transplated tumor of human pancreatic cancer PANC-1 was established and randomly divided into 6 groups for conducting the experiment： sterile normal saline group, TLR9 agonist, TLR9 inhibitor group, gemcitabine group, TLR9 inhibitor plus gemcitabine Bin group,TLR9 agonist plus gemcitabine. The tumor size and growth situation were recorded by the vernier caliper. The immunohistoehemical method was used to detect tumor TLR9 receptor expres- sion. The tumor growth, metastasis and paracaneerous tissue invasion situation were observed by the magnetic resonance imaging （MRI）. Results The volume and growth speed of resected tumor mass in the gemcitabine group, TLR9 agonist t getncitabme group,TLR9 inhibitor plus gemcitabine group was significantly smaller than those in other groups （P〈0.05） ,which in the TLR9 agonist ± gemcitabine group were significantly greater than those in the TLR9 inhibitor plus gemcitabine group and gemcitabine group （P〈0.05）, the difference between the TLR9 inhibitor plus gemcitabine group and gemcitabine group had statistical signifi- cance （P〈0.05） ,while the difference among the TLR9 agonist group.TLR9 inhibitor group and normal saline group had no stas- tistical significance （P〉0.05）. The tumor in mice at 7 weeks after planting showed oval shape with clear boundary by MRI obser- vation,no obvious metastais and paracancerous invasion were seen m paracancerous tissues no statistically significant, 5 weeks, 6 weeks after planting, seven weeks mice observed in MRI,the tumor into an, state clearly that the transfer of the surrounding tissue, no significant vascular invasion,heart,liver, kidney disease. The TLR9 expression on the surface of tumor tissue was detected and i- dentified. Conclusion Pancreatic cancer nude mouse transplated tumor has definitely positive expression of TLR9 ,TLR9 activation can signifi

关 键 词：胰腺肿瘤 裸鼠 吉西他滨 TLR9 

分 类 号：R735.9[医药卫生—肿瘤]