骨形态发生蛋白9对人乳腺癌MDA-MB-231细胞增殖和凋亡的影响

Effects of bone morphogenetic protein 9 on the proliferation and apoptosis of breast cancer MDA-MB-231 cells

目的:探讨骨形态发生蛋白9(bone morphogenetic protein9,BMP9)在体内、外对人乳腺癌MDA-MB-231细胞增殖和凋亡的影响。方法:将pAdtrack-CMV/BMP9和pAdtrack-CMV/GFP腺病毒感染MDA-MB-231细胞,RT-PCR法检测MDA-MB-231/GFP和MDA-MB-231/BMP9细胞中BMP9mRNA的表达,MTT法、平板集落形成实验和FCM法检测细胞增殖和凋亡的情况。建立裸鼠MDA-MB-231、MDA-MB-231/GFP和MDA-MB-231/BMP9移植瘤模型,测量移植瘤体积,TUNEL法检测肿瘤细胞的凋亡情况。结果:MDA-MB-231和MDA-MB-231/GFP细胞中无BMP9mRNA的表达,MDA-MB-231/BMP9细胞中有明显BMP9mRNA表达;MDA-MB-231/BMP9细胞增殖抑制率高于MDA-MB-231/GFP细胞(P<0.05),而细胞集落形成率明显低于MDA-MB-231/GFP和MDA-MB-231组(P<0.05),细胞凋亡率则明显高于MDA-MB-231/GFP和MDA-MB-231组(P<0.05)。MDA-MB-231/BMP9组的裸鼠移植瘤体积明显小于MDA-MB-231/GFP和MDA-MB-231组(P<0.001),而移植瘤细胞中的凋亡指数则明显高于MDA-MB-231/GFP和MDA-MB-231组(P<0.001)。结论:BMP9可在体内、外抑制人乳腺癌MDA-MB-231细胞增殖并促进其凋亡。

Objective： To investigate the effects of bone morphogenetic protein 9 （BMP9） on the proliferation and apoptosis of breast cancer MDA-MB-231 cells in vitro and in vivo. Methods： MDA-MB-231 cells were infected with pAdtrack-CMV/BMP9 or pAdtrack-CMV/GFP adenovirus. The expression levels of BMP9 mRNA in MDA-MB-231/GFP and MDA-MB-231/BMP9 cells were detected by RT-PCR. The proliferation inhibitory rate and the apoptosis rate of breast cancer cells were determined by MTT assay, colony-forming assay and flow cytometry method. Then the breast cancer MDA-MB-231, MDA-MB-231/GFP or MDA-MB-231/BMP9 xenografts in nude mice were established. The volume of xenograft tumor was measured, and the apoptosis rate was detected by TUNEL assay. Results： There was no expression of BMP9 mRNA in MDA-MB-231 and MDA-MB-231/GFP cells, but the expression of BMP9 mRNA in MDA-MB-231/BMP9 cells was significant. The proliferation inhibitory rate of MDA-MB-231/BMP9 cells was higher than that of MDA-MB-231/GFP cells （P0.05）. The colony-forming rate of MDA-MB-231/BMP9 cells was lower than those of MDA-MB-231/GFP and MDA-MB-231 cells （P0.05）. The apoptosis rate of MDA-MB-231/BMP9 cells was higher than those of MDA-MB-231/GFP and MDA-MB-231 cells （P0.05）. The xenograft tumor volume in the MDA-MB-231/BMP9 group was smaller than those in the MDA-MB-231/GFP and MDA-MB-231 groups （P0.001）. The apoptosis index of xenograft tumor in the MDA-MB-231/BMP9 group was higher than those in the MDA-MB-231/GFP and MDA-MB-231 groups （P0.001）. Conclusion： BMP9 can inhibit the proliferation ability and induce the apoptosis of MDA-MB-231 cells in vitro and in vivo.