摘要
目的研究山楂酸(maslinic acid,MA)对人肺癌细胞增殖、迁移和其诱导的破骨细胞分化的调控作用和可能的作用机制。方法应用山楂酸处理肺癌细胞株,MTS法检测细胞活性的抑制率;通过Transwell观察肺癌细胞的迁移;收集山楂酸刺激肺癌细胞后的培养基并观察其对破骨细胞分化的诱导作用;并通过PCR实验检测可能靶基因m RNA的水平改变。结果山楂酸对正常肺上皮细胞HBE无明显抑制作用,但可显著抑制肺腺癌细胞A549、PC9和H1299的增殖和迁移,且抑制作用和药物浓度呈正相关;20μmol/L的山楂酸对A549、PC9和H1299细胞增殖的抑制率分别为29%、58%和22%,而40μmol/L的抑制率为68%、82%和66%。同时山楂酸可显著抑制由A549细胞诱导的BMM细胞向破骨细胞的分化(P<0.001);通过PCR实验,本研究结果显示山楂酸可抑制NF-κb通路下游BCL2、MMP2和MMP9的m RNA水平,并促进BAX、CASP3和CASP8等凋亡相关m RNA水平。结论山楂酸可显著抑制肺癌细胞的增殖及迁移,并抑制由肺癌细胞诱导的破骨细胞分化,这种抑制作用可能是通过抑制NF-κb通路和激活线粒体凋亡通路实现的。
Objective To investigate the effects of maslinic acid （ MA ） on lung cancer cell proliferation, migration and the induction role to osteoclasstogenesis, and further explore the possible molecular mechanisms of MA in lung cancer cells.Methods Lung cancer cell lines were treated with MA. Then, the cell proliferation rates were detected by MTS assay, while the migration of the tumor cell was examined by transwell assay. The condition medium from A549 cells stimulated by MA was collected, and then was used in BMM culture to observe the osteoclastogenesis. The mRNA levels of the possible targets of MA were detected by PCR assay.Results MA showed no significant inhibition on HBE cells, however, it signiifcantly suppressed the proliferation and migration of A549, PC9 and H1299 cells with a positive correlation of the MA concentration. 20 μmol / L of MA suppressed the proliferation of A549, PC9 and H1299 cell proliferation with ratios of 29%, 58% and 22%, while the inhibition ratios of 40 μmol / L MA were 68%, 82% and 66% respectively. Furthermore, MA obviously inhibited osteoclast differentiation induced by A549 cells （P〈0.001 ）. In addition, It was found that MA decreased the mRNA level of BCL2, MMP2 and MMP9 which were the downstream of NF-κb pathway, while it increased the mRNA level of BAX, CASP3 and CASP8 which were the key components of the mitochondrial apoptotic pathway.Conclusions MA can signiifcantly suppress proliferation and migration of lung cancer cells, as well as the osteoclastogenesis induced by lung cancer cells. Roles of MA in lung cancer cells are possibly achieved through the NF-κb pathway and the mitochondrial apoptotic pathway.
出处
《中国骨与关节杂志》
CAS
2015年第9期706-712,共7页
Chinese Journal of Bone and Joint
基金
上海市自然科学基金面上项目(STCSM
12ZR1439200)
上海市优秀青年医学人才培养计划(XYQ2013099)
关键词
山楂酸
细胞运动
破骨细胞
细胞分化
肺肿瘤
Maslinic acid
Cell Movement
Osteoclasts
Cell differentiation
Lung neoplasms
