肺耐药蛋白LRP在肺癌中的表达及意义  

The expression and significance of lung resistance protein in lung cancer

作　　者：李杰[1] 龚民[1] 崔永[1] 李浩[1] 常栋[1] 林昌锦[1] 高志[1] 胡健[1] 王天佑[1] 

机构地区：[1]首都医科大学附属北京友谊医院胸外科,北京100050

出　　处：《现代肿瘤医学》2014年第12期2875-2879,共5页Journal of Modern Oncology

摘　　要：目的:检测LRP在不同分化阶段肺癌组织中的表达,探讨肺癌分化与LRP之间的关联;干扰LRP后,观察其对肺癌细胞A549侵袭能力的影响及其可能的分子机制。方法:应用免疫荧光检测肺癌组织中LRP蛋白及表达分布,Western blot检测肺癌组织及癌旁组织中LRP蛋白表达。通过RNAi技术干扰LRP后,运用RT-PCR、Western blot技术,观察干扰LRP基因效率,检测LRP在A549细胞的表达及对细胞侵袭能力的影响;同时用Western blot方法检测ERK及AKT信号通路、MMP金属蛋白酶及凋亡蛋白的表达。结果:肺癌中LRP阳性率与组织学分级相关,在低分化、中分化、高分化肺癌组织及癌旁组织中表达率分别为60.6%、39.3%、18.3%、8.3%,肺癌组织中LRP蛋白表达量明显高于癌旁组织。LRP-siRNA转染组侵袭率为(60.4±6.4)%高于对照组的(50.5±4.4)%,差异显著(P<0.05)。LRP-siRNA转染组AKT和ERK1/2磷酸化水平明显下降;MMP-2和MMP-9蛋白的表达水平受到抑制;凋亡相关蛋白Bcl-2降低,Bax升高。结论:LRP表达与肺癌的组织学分级有关,LRP蛋白有可能是肺癌浸润和转移的一个重要参考指标,可为肺癌治疗提供潜在的靶点。Objective： To detect the expression of lung resistance protein（ LRP） in the different differentiations of lung cancer tissues and to study the mechanism of invasion of A549 cells affected by LRP. Methods： The expression of LRP was detected by immunofluoresence in lung cancer tissue and the tissue around edge of the cancer. The protein level of LRP in lung cancer tissues was detected by using Western blot. The effect of LRP expression on A549 cells was observed by using RT- PCR and Western blot. The abilities of invasion and metastasis were evaluated by transwell invasion and migration assay in vitro. The protein expression of ERK,AKT,MMP- 2,MMP- 9,Bcl- 2,and Bax was measured by Western blot. Results： The positive expression rate of LRP was 60. 6% in low- grade differentiation of lung cancer,39. 3% in middle- grade differentiation of lung cancer,18. 3% in high- grade lung cancer and 8. 3%in adjacent tissue by immunofluoresence. LRP expression levels in the different differential lung cancer tissues were significantly higher than that in adjacent tissues by Western blot. The rate of migration and invasion in LRP- siRNA group was（ 60. 4 ± 6. 4） % compared to（ 50. 5 ± 4. 4） % in the control group,there was a significant difference（ P 0. 05）. Active AKT and ERK,MMP- 2,MMP- 9,and Bcl- 2 were suppressed,and Bax was upregulated when LRP was inhibited. Conclusion： The expression level of LRP is closely related to differentiation of the lung cancer. LRP may be one of important indicators involved in lung cancer infiltrated and transferred. LRP might be one of potential targets for lung cancer treatment.

关 键 词：肺耐药蛋白 肺癌 侵袭 机制 

分 类 号：R734.2[医药卫生—肿瘤]