目的:探讨参慈胶囊对人肺腺癌A549/DDP裸鼠体内多药耐药相关基因的影响。方法:将50只C57BL/6小鼠接种人肺腺癌细胞A549/DDP细胞悬液建立实体瘤模型,随机分为对照组、参慈胶囊组、参慈胶囊+顺铂组、顺铂组,各10只。对照组予等量生理盐水...目的:探讨参慈胶囊对人肺腺癌A549/DDP裸鼠体内多药耐药相关基因的影响。方法:将50只C57BL/6小鼠接种人肺腺癌细胞A549/DDP细胞悬液建立实体瘤模型,随机分为对照组、参慈胶囊组、参慈胶囊+顺铂组、顺铂组,各10只。对照组予等量生理盐水,其余各组荷瘤小鼠均用药21 d,断颈处死取肿瘤组织,采用FQ-PCR技术检测人肺腺癌A549/DDP肺癌组织MDR1、MRP1、LRP m RNA的表达情况。结果:MDR1 m RNA、MRP1 m RNA、LRP1 m RNA在各组均有表达,各治疗组的MDR1m RNA、MRP1 m RNA、LRP1 m RNA均低于对照组,差异均有统计学意义(P<0.01);参慈胶囊+顺铂组的MDR1 m RNA、MRP1 m RNA、LRP1 m RNA的表达均明显低于参慈胶囊组和顺铂组,差异均有统计学意义(P<0.01)。结论:通过降低MDR1、MRP1、LRP多药耐药相关基因的表达,可能是参慈胶囊逆转人肺腺癌A549/DDP裸鼠体内多药耐药的作用机制之一。展开更多
AIM:To investigate the effect of the G-1666A polymorphism in the multidrug resistance related protein-1 (MRP1) on outcome of hepatocellular carcinoma (HCC). METHODS:A cohort of 162 patients with surgically resected HC...AIM:To investigate the effect of the G-1666A polymorphism in the multidrug resistance related protein-1 (MRP1) on outcome of hepatocellular carcinoma (HCC). METHODS:A cohort of 162 patients with surgically resected HCC who received no postsurgical treatment until relapse was studied. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. Electrophoretic mobility shift assay (EMSA) was used to evaluate the influence of the G-1666A polymorphism on the binding affinity of the MRP1 promoter with its putative transcription factors. RESULTS:Kaplan-Meier analysis showed that patients with GG homologues had a reduced 4-year disease-free survival compared with those carrying at least one A allele (P = 0.011). Multivariate Cox regression analysis indicated that the-1666GG genotype represented an independent predictor of poorer disease-free survival [hazard ratio (HR) = 3.067,95% confidence interval (CI):1.587-5.952,P = 0.001],and this trend became worse in men (HR = 3.154,95% CI:1.604-6.201,P = 0.001). A similar association was also observed between 4-year overall survival and the polymorphism in men (HR = 3.342,95% CI:1.474-7.576,P = 0.004). Moreover,EMSA suggested that the G allele had a stronger binding affinity to nuclear proteins. CONCLUSION:The MRP1-1666GG genotype predicted a worse outcome and was an independent predictor of poor survival in patients with HCC from Southeast China.展开更多
目的:观察Ⅰα亚型c GMP依赖性蛋白激酶(c GMP-dependent protein kinaseⅠα,PKGⅠα)和Ⅱ型c GMP依赖性蛋白激酶(PKGⅡ)对肺癌细胞顺铂耐药的影响。方法:用编码PKGⅠα和PKGⅡc DNA的腺病毒载体感染A549/DDP细胞,使其高表达PKGⅠα和...目的:观察Ⅰα亚型c GMP依赖性蛋白激酶(c GMP-dependent protein kinaseⅠα,PKGⅠα)和Ⅱ型c GMP依赖性蛋白激酶(PKGⅡ)对肺癌细胞顺铂耐药的影响。方法:用编码PKGⅠα和PKGⅡc DNA的腺病毒载体感染A549/DDP细胞,使其高表达PKGⅠα和PKGⅡ并以相应激活剂激活,用CCK8试剂盒检测顺铂作用后肺癌细胞的增殖活性,蛋白质印迹法检测PKGs对A549/DDP细胞多药耐药性蛋白1(multidrug resistance protein 1,MRP1)和肺耐药相关蛋白(lung resistance related protein,LRP)表达的影响。结果:PKGⅠα和PKGⅡ表达增高并被激活后,均可加强顺铂对A549/DDP细胞增殖的抑制,并明显降低A549/DDP细胞MRP1和LRP的表达。结论:PKGⅠα和PKGⅡ可通过降低耐药相关蛋白MRP1和LRP的表达,抑制A549/DDP细胞的耐药活性,发挥抗癌作用。展开更多
文摘目的:探讨参慈胶囊对人肺腺癌A549/DDP裸鼠体内多药耐药相关基因的影响。方法:将50只C57BL/6小鼠接种人肺腺癌细胞A549/DDP细胞悬液建立实体瘤模型,随机分为对照组、参慈胶囊组、参慈胶囊+顺铂组、顺铂组,各10只。对照组予等量生理盐水,其余各组荷瘤小鼠均用药21 d,断颈处死取肿瘤组织,采用FQ-PCR技术检测人肺腺癌A549/DDP肺癌组织MDR1、MRP1、LRP m RNA的表达情况。结果:MDR1 m RNA、MRP1 m RNA、LRP1 m RNA在各组均有表达,各治疗组的MDR1m RNA、MRP1 m RNA、LRP1 m RNA均低于对照组,差异均有统计学意义(P<0.01);参慈胶囊+顺铂组的MDR1 m RNA、MRP1 m RNA、LRP1 m RNA的表达均明显低于参慈胶囊组和顺铂组,差异均有统计学意义(P<0.01)。结论:通过降低MDR1、MRP1、LRP多药耐药相关基因的表达,可能是参慈胶囊逆转人肺腺癌A549/DDP裸鼠体内多药耐药的作用机制之一。
基金Supported by The Scientific and Technological Program of Guangdong Province, China, No. 2003B30102
文摘AIM:To investigate the effect of the G-1666A polymorphism in the multidrug resistance related protein-1 (MRP1) on outcome of hepatocellular carcinoma (HCC). METHODS:A cohort of 162 patients with surgically resected HCC who received no postsurgical treatment until relapse was studied. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. Electrophoretic mobility shift assay (EMSA) was used to evaluate the influence of the G-1666A polymorphism on the binding affinity of the MRP1 promoter with its putative transcription factors. RESULTS:Kaplan-Meier analysis showed that patients with GG homologues had a reduced 4-year disease-free survival compared with those carrying at least one A allele (P = 0.011). Multivariate Cox regression analysis indicated that the-1666GG genotype represented an independent predictor of poorer disease-free survival [hazard ratio (HR) = 3.067,95% confidence interval (CI):1.587-5.952,P = 0.001],and this trend became worse in men (HR = 3.154,95% CI:1.604-6.201,P = 0.001). A similar association was also observed between 4-year overall survival and the polymorphism in men (HR = 3.342,95% CI:1.474-7.576,P = 0.004). Moreover,EMSA suggested that the G allele had a stronger binding affinity to nuclear proteins. CONCLUSION:The MRP1-1666GG genotype predicted a worse outcome and was an independent predictor of poor survival in patients with HCC from Southeast China.
文摘目的:观察Ⅰα亚型c GMP依赖性蛋白激酶(c GMP-dependent protein kinaseⅠα,PKGⅠα)和Ⅱ型c GMP依赖性蛋白激酶(PKGⅡ)对肺癌细胞顺铂耐药的影响。方法:用编码PKGⅠα和PKGⅡc DNA的腺病毒载体感染A549/DDP细胞,使其高表达PKGⅠα和PKGⅡ并以相应激活剂激活,用CCK8试剂盒检测顺铂作用后肺癌细胞的增殖活性,蛋白质印迹法检测PKGs对A549/DDP细胞多药耐药性蛋白1(multidrug resistance protein 1,MRP1)和肺耐药相关蛋白(lung resistance related protein,LRP)表达的影响。结果:PKGⅠα和PKGⅡ表达增高并被激活后,均可加强顺铂对A549/DDP细胞增殖的抑制,并明显降低A549/DDP细胞MRP1和LRP的表达。结论:PKGⅠα和PKGⅡ可通过降低耐药相关蛋白MRP1和LRP的表达,抑制A549/DDP细胞的耐药活性,发挥抗癌作用。
