| 肖华平,谢 辉,罗春阳.RNA干扰沉默DcR3对人胰腺癌细胞裸鼠移植瘤放疗增敏的实验研究[J].肿瘤学杂志,2017,23(12):1079-1084. |
| RNA干扰沉默DcR3对人胰腺癌细胞裸鼠移植瘤放疗增敏的实验研究 |
| Effect of Interference RNA Silencing DcR3 on Radiotherapy of Human Pancreatic Cancer Cell Xenografts in Nude Mice |
| 投稿时间：2017-03-14 |
| DOI：10.11735/j.issn.1671-170X.2017.12.B007 |
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| 中文关键词: 胰腺肿瘤 诱骗受体3 RNA干扰 放疗敏感性 凋亡 |
| 英文关键词:pancreatic cancer decoy receptor 3 RNA interference radiosensitivity apoptosis |
| 基金项目:湖南省自然科学基金 (14JJ3136)；郴州市科技局基金(CZ2013096) |
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| 中文摘要: |
| 摘 要：［目的］探讨RNA干扰沉默DcR3对人胰腺癌细胞裸鼠移植瘤放疗敏感性的影响及其可能机制。［方法］ 取对数生长期的AsPC-1细胞 1×107/ml，接种于6周龄裸鼠左后肢腹股沟，当皮下肿瘤直径为8mm左右时，随机分为4组(n=15)：PBS组、DcR3siRNA组、放疗组（RT）和DcR3siRNA+放疗组（DcR3siRNA+RT），观察DcR3siRNA联合放疗对人胰腺癌AsPC-1细胞裸鼠移植瘤的治疗效果；应用ELISA和Western blot检测各组DcR3的蛋白表达变化；免疫组织化学和Western blot分析各组Caspase-8和Caspase-3蛋白表达的变化；TUNEL检测各组肿瘤细胞凋亡情况。［结果］ DcR3siRNA+RT组较其他各组更能抑制移植瘤的生长，DcR3-siRNA+RT对肿瘤的抑制率明显高于单纯RT组，与RT组相比，DcR3siRNA+RT组的抑瘤率为80.86%±4.17%；DcR3siRNA+RT组的DcR3蛋白量和蛋白相对表达均明显低于RT组，差异有统计学意义(P＜0.05)；DcR3siRNA+RT组的Caspase-8和Caspase-3蛋白表达均明显高于单独RT组；DcR3siRNA组、RT组以及DcR3-siRNA+RT组肿瘤组织内均可观察到凋亡细胞，而DcR3siRNA+RT组肿瘤细胞凋亡数目明显高于RT组或DcR3siRNA组。［结论］RNA干扰沉默DcR3基因可以增加人胰腺癌细胞裸鼠移植瘤对放疗的敏感性，该作用可能与沉默DcR3可激活Caspase-8/Caspase-3凋亡途径和促进肿瘤细胞凋亡有关。 |
| 英文摘要: |
| Abstract：［Objective］ To investigate the effect of RNA interference silencing DcR3 on radiotherapy sensitivity of human pancreatic cancer cell xenografts and its possible mechanism. ［Methods］ 1×107/mL of AsPC-1 cells in the logarithmic growth phase were inoculated into the left hind limb groin of nude mice. When the diameter of subcutaneous tumor was about 8mm，the tumor bearing nude mice were randomly divided into four groups (n=15 for each)：PBS，DcR3siRNA，radiotherapy and DcR3siRNA + radiotherapy. The therapeutic effect of DcR3siRNA combined with radiotherapy was observed in nude mice transplanted with human pancreatic cancer AsPC-1. The protein expression of DcR3 was detected by ELISA and Western blot. The expression of Caspase-8 and Caspase-3 protein was detected by Western blot and immunohistochemistry. TUNEL was used to detect the apoptosis of tumor cells. ［Results］ The inhibition rate of DcR3siRNA+ RT was significantly higher than that of DcR3siRNA and RT alone (94.53±3.17%，46.87±3.58% and 70.68±4.36，respectively，χ2=9.136，P=0.011). DcR3 protein expression in DcR3siRNA+RT group was significantly lower than that in RT group (P＜0.01). The expressions of Caspase-8 and Caspase-3 in DcR3siRNA+RT group were significantly higher than those in RT group(P＜0.01). The number of apoptotic cells in DcR3siRNA+RT group was significantly higher than that in RT group or DcR3siRNA group. Conclusion：RNA interference silencing DcR3 can increase the sensitivity of pancreatic cancer to radiotherapy，which may be related to activation of Caspase-8/Caspase-3 apoptosis pathway and promoting tumor cell apoptosis. |
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