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GRP94表达在肺癌细胞对VP-16化疗耐药中的作用
张黎川 1,2, 王佳瑞3, 孟强2, 李恩成2, 王 琪4
1.大连大学 附属中山医院 呼吸内科,辽宁 大连 116001;2.大连医科大学 研究生院,辽宁 大连 116044;3.大连市第五人民医院 肿瘤内科,辽宁 大连 116021;4.大连医科大学 附属第二医院 呼吸内科,辽宁 大连 116027
摘要:
[目的]检测在Ca2+拮抗剂A23187诱导下,人肺腺癌细胞SPCA1中GRP94的表达水平,并分析其表达在肺癌细胞对VP-16耐药中的作用。[方法]采用RT-PCR、免疫荧光细胞化学方法检测不同浓度A23187处理组细胞的GRP94核酸及蛋白表达,用MTT法测定细胞在VP-16作用下的生存率。[结果]A23187可明显诱导SPCA1细胞GRP94核酸和蛋白表达,且表达水平随A23187呈浓度依赖性增加。MTT法测定结果显示:诱导组细胞(A23187浓度为0.5~6 μmol/L)对VP-16的IC50值明显高于对照组,而且IC50值的升高亦对A23187呈一定的浓度依赖性,当A23187浓度为6 μmol/L时 IC50值最大。[结论]GRP94的表达与肺腺癌细胞SPCA1对VP-16的耐药性有关,有针对性地抑制GRP94基因表达或功能可能成为肺癌治疗的新方法。
关键词:  GRP94  人类肺腺癌系  VP-16耐药
DOI:10.11724/jdmu.2011.03.03
分类号:R34
基金项目:
Expression of GRP94 and its function in chemotherapy resistance to VP-16 in human lung cancer cell line SPCA1
ZHANG Li-chuan1,2, WANG Jia-rui3, MENG Qiang2, LI En-cheng2, WANG Qi4
1.Department of Respiratory,the Affiliated Zhongshan Hospital of Dalian University,Dalian 116001,China;2.Graduate School,Dalian Medical University,Dalian 116044,China;3.Department of Oncology,the Fifth Hospital of Dalian,Dalian 116021,China;4.Department of Respiratory,the Second Affiliated Hospital of Dalian Medical University,Dalian 116027,China
Abstract:
[Objective]To investigate the expression of GRP94 under the induction of A23187 and its function in drug resistance to VP-16 in human lung cancer cell line SPCA1.[Methods]RT-PCR and Immunofluorescence were employed in analyzing the expression of GRP94 at mRNA and protein in SPCA1 cells treated with A23187 at different concentration (0,0.5,1.0,1.5,2.0, 4.0,6.0 μmol/L).Cell survival rate following VP-16 treatment was determined with MTT assay.[Results]To a certain extent,the expression of GRP94 at both mRNA and protein level was significantly,exhibiting up-regulated by A23187 a dose-dependent manner.The mRNA expression of GPR94 was elevated up to 0.7~4.3 folds,compared to the control.The IC50s to VP-16 also showed a substantial elevation for the cells induced by A23187 at different concentrations.Survival curves analysis showed that the A23187 induction caused a significant prolonged survival for the cells subjected to VP-16 (P<0.05).[Conclusions]Up-regulated GRP94 is associated with the chemoresistance of SPCA1 cells to VP-16.
Key words:  GRP94  human lung adenocarcinoma  VP-16 resistance