RNA干扰HSF1增强碘125粒子放疗裸鼠胰腺癌移植瘤敏感性的分析  

Effect of siRNA Silencing of HSF1 on Iodine-125 Particle Radio-treating Human Pancreatic Cancer Xenograft in Nude Mice

作　　者：龚敏 王爱萍 王桂良 邱萍 徐林芳 李兴 文剑波[1] GONG Min;WANG Aiping;WANG Guiliang(Gannan Medical University Affiliated Pingxiang Hospital,Pingxiang,337000)

机构地区：[1]赣南医学院附属萍乡医院,337000

出　　处：《实用癌症杂志》2022年第12期1915-1919,1925,共6页The Practical Journal of Cancer

基　　金：江西省卫生健康委课题(编号:202212166)。

摘　　要：目的探讨siRNA沉默HSF1基因对碘125粒子放疗裸鼠胰腺癌移植瘤效果的影响。方法分别将空白胰腺癌细胞株及稳定转染的HSF1沉默的胰腺癌细胞株注射入裸鼠背部皮下,建立裸鼠胰腺癌移植瘤模型各8只。每组取4只继续自然生长,另4只给予碘125粒子放疗。20 d后处死裸鼠取瘤体,称重、计算抑瘤率、病理切片分析苏木精-伊红染色坏死评分、Tunel染色分析凋亡指数、QRT-PCR检测mRNA表达、Western blot检测蛋白质表达。结果HSF1蛋白在空白细胞组中表达较高,而ShRNA-HSF1组中表达较弱,差异有统计学意义。与空白细胞组比较,ShRNA-HSF1组的体积增量比和瘤重显著性降低,抑瘤率和凋亡指数显著性升高。在自然生长条件下,ShRNA-HSF1能抑制Bcl2 mRNA和蛋白的表达,而促进Bax与Caspase 3 mRNA和蛋白的表达,经碘125粒子放疗后,Bcl2 mRNA和蛋白表达降低,而Bax与Caspase 3 mRNA和蛋白表达升高,ShRNA-HSF1进一步促进Bcl2蛋白表达降低,而进一步促进Bax和Caspase 3 mRNA蛋白表达升高。结论RNA干扰HSF1能抑制胰腺癌移植瘤生长,碘125粒子能诱导胰腺癌移植瘤凋亡,沉默HSF1能通过抑制Bcl2 mRNA和蛋白、促进Bax和Caspase 3 mRNA和蛋白的表达,从而增强碘125放疗胰腺癌移植瘤的敏感性。Objective To investigate the effect of Effect of siRNA silencing ofHSF1on iodine-125 particle radio-treating human pancreatic cancer xenograft in nude mice.Methods Blank pancreatic cancer cell lines and stably transfectedHSF1silent pancreatic cancer cell lines were injected into the subcutaneous back of nude mice respectively,and 8 pancreatic cancer xenograft models were established.Four in each group continued to grow naturally,and four in each group received iodine-125 particle radiotherapy.20 days later,the nude mice were sacrificed for tumor collection,weighed,and the tumor inhibition rate was calculated.Pathological sections were analyzed for necrosis score by HE staining and apoptosis index by Tunel staining.Results HSF1protein expression was higher in blank group,but lower in ShRNA-HSF1group,the difference was statistically significant.Compared with blank group,volume increment ratio and tumor weight significantly decreased,while tumor inhibition rate and apoptosis index significantly increased in the ShRNA-HSF1group.ShRNA-HSF1can inhibit the expression of Bcl2 mRNA and protein and promote the expression of Bax and Caspase 3 mRNA and protein under natural growth condition.After iodine 125 particle radiotherapy,the expression of Bcl2 mRNA and protein decreased while the expression of Bax and Caspase 3 mRNA and protein increased.ShRNA-HSF1further reduced the expression of Bcl2 mRNA and protein,and further increased the expression of Bax and Caspase 3 mRNA and protein.Conclusion RNA interferenceHSF1can inhibit the growth of pancreatic cancer xenografts,iodine-125 can induce the apoptosis of pancreatic cancer xenografts,and silencingHSF1can promote the sensitivity of pancreatic cancer xenografts by inhibiting the expression of Bcl2 mRNA and protein and promoting the expression of Bax and Caspase 3 mRNA and protein.

关 键 词：胰腺癌 HSF1 碘125粒子 放疗 

分 类 号：R735.9[医药卫生—肿瘤]