抗人乙酰肝素酶单克隆抗体联合紫杉醇对人乳腺癌细胞增殖、迁移和侵袭的影响  

Effects of anti-heparanase monoclonal antibody in combination with paclitaxel on proliferation, migration and invasion of breast cancer cell lines

作　　者：郭莹[1] 罗雅玥 董斌[1] 段涛[1] 林月霞[1] 田素娟[1] 

机构地区：[1]广东药学院生命科学与生物制药学院生物科学系,广东广州510006

出　　处：《肿瘤》2015年第6期630-638,共9页Tumor

摘　　要：目的 :探讨抗人乙酰肝素酶(heparanase,HPA)单克隆抗体(简称单抗)联合紫杉醇(paclitaxel,PTX)对乳腺癌MCF-7、MCF-7/F5和MDAMB-231细胞增殖、迁移和侵袭的影响。方法 :应用反转录-PCR(reverse transcription-PCR,RT-RCR)法检测抗人HPA单抗对MCF-7、MCF-7/F5和MDA-MB-231细胞HPA m RNA表达水平的影响;MTT法检测不同浓度的抗人HPA单抗、PTX或抗人HPA单抗联合PTX干预对乳腺癌细胞增殖能力的影响;FCM法、细胞划痕实验和Transwell小室法分别检测抗人HPA单抗、PTX或抗人HPA单抗联合PTX干预对乳腺癌细胞的细胞周期、细胞迁移和细胞侵袭能力的影响。结果:10和20 nmol/L抗人HPA单抗干预后,MCF-7/F5和MDAMB-231细胞中HPA m RNA的表达水平明显低于鼠Ig G组(P值均<0.05)。抗人HPA单抗和PTX单独处理后,MCF-7、MCF-7/F5和MDAMB-231细胞的增殖受到抑制,且呈剂量依赖性(P值均<0.05)。抗人HPA单抗联合PTX处理后,3组细胞的增殖抑制率均高于任一单药处理组(P值均<0.05)。抗人HPA单抗联合PTX处理后,3组细胞中G0/G1期细胞所占百分比明显低于溶剂对照组(只加培养液),G2/M期细胞所占百分比明显高于溶剂对照组(P<0.05,P<0.01),且出现亚二倍体峰。抗人HPA单抗合PTX处理后,MCF-7/F5和MDA-MB-231细胞的迁移能力和侵袭能力低于溶剂对照组、鼠Ig G组和任一单药处理组(P值均<0.05)。结论 :抗人HPA单抗联合PTX可协同抑制乳腺癌细胞的增殖、迁移和侵袭能力,其作用机制可能与二药联合作用后将细胞阻滞于G2/M期有关。Objective： To investigate the effects of anti-heparanase monoclonal antibody（anti-HPA m Ab） in combination with paclitaxel（PTX） on proliferation, migration and invasion of breast cancer MCF-7, MCF-7/F5 and MDA-MB-231 cells.Methods： The expression levels of HPA m RNA in MCF-7, MCF-7/F5 and MDA-MB-231 cells after treatment with anti-HPA m Ab were detected by reverse transcription-PCR（RT-PCR）. The proliferation of the three breast cancer cell lines after treatment with different concentrations of anti-HPA m Ab or PTX alone or in combination was detected by MTT assay. The cell cycle distribution and the abilities of migration and invasion of these breast cancer cells after different treatment modalities were examined by flow cytometry（FCM）, wound healing assay and Transwell assay, respectively.Results： The expression levels of HPA m RNA in MCF-7/F5 and MDA-MB-231 cells after treatment with 10 and 20 nmol/L anti-HPA m Ab were lower than those of murine immunoglobulin G（Ig G） treatment group（all P 〈 0.05）. The proliferation of MCF-7, MCF-7/F5 and MDA-MB-231 cells after treatment with anti-HPA m Ab or PTX alone was inhibited in a concentration-dependent manner（all P 〈 0.05）. The proliferative inhibition rates of the three breast cancer cell lines after treatment with combination of anti-HPA m Ab and PTX were higher than those of any single drug treatment groups（all P 〈 0.05）. The ratios of G0/G1 phase of the three breast cancer cell lines after treatment with combination of anti-HPA m Ab and PTX were lower than those of the control groups（three breast cancer cell lines without any treatment）, and the ratios of G2/M phase were opposite（P 〈 0.05, P 〈 0.01）, with a typical sub-diploid peak which appeared before G0/G1 phase. The abilities of migration and invasion of MCF-7/F5 and MDAMB-231 cells after treatment with combination of anti-HPA m Ab and PTX were lower than those of the control, murine Ig G and single drug treatment groups（all P 〈 0.05）.Conclusion： A

关 键 词：乳腺肿瘤 抗体 单克隆 细胞增殖 乙酰肝素酶 紫杉醇 MCF-7细胞 MDA-MB-231细胞 

分 类 号：R737.9[医药卫生—肿瘤]