摘要
目的 探讨唑来膦酸（z0L）联合阿霉素（ADM）对胃癌SGC7901细胞株增殖、侵袭和黏附的影响。方法采用MTT法检测不同浓度的唑来膦酸和阿霉素对胃癌细胞株SGC-7901的增殖和细胞黏附作用；Transwell实验分析药物对细胞侵袭能力的影响；Real—timePCR检测药物对细胞株MMP-2、TIMP-2、MMP-9、ICAM-1和CD44mRNA表达的影响。结果唑来膦酸浓度10、10～、10～、10-3mol／L作用于SGC-7901细胞48h后，细胞生长抑制率分别为4．98％、12．19％、27．34％、73．13％，与对照组比较，抑制率均显著升高（P〈0．01），且抑制作用随着剂量的升高和时间的延长而增强（P〈0．05）；10μmol／1浓度的唑来膦酸和0．5mg／L浓度的阿霉素单独以及联合用药作用于细胞，观察2h、4h、6h后，黏附率分别为：5．03％、24．38％、59．65％；4．40％、19．77％、51．22％；4．28％、18．62％、51．02％；4．02％、15．02％、46．95％，与对照组比较，加入药物后，细胞的黏附能力有不同程度的降低（P〈0．05），且呈时间依赖性，但联合用药组与相应浓度单药组比较差异无统计学意义（P〉0．05）；上述浓度的药物作用于细胞，每个高倍视野细胞数（个）分别为：105．11±10．43、98．37±15．75、96．194-9．24、83．02±19．72，与对照组比较，单药有减弱侵袭力的趋势，但作用较弱（P〉0．05），联合用药时，细胞的侵袭能力则明显下降（P〈0．05）；唑来膦酸和阿霉素单药均有降低CD44、MMP-2、MMP-9、ICAM-1mRNA和升高TIPM-2mRNA表达水平的作用，联合用药后该作用则表现更为显著（P〈0．05或P＜0．01）。结论唑来膦酸和阿霉素对人胃癌细胞株SGC-7901具有一定的抑制增殖、降低细胞黏附和侵袭能力的作用，且两药联合具有协同抗肿瘤作用，可能和下调ICAM-1、MMP2、MMP-9、CD44mRNA的表达以及上调TIMP2mRNA的表达水平相关。
Objective To explore the possible effect of combined treatment of zoledronic acid and doxorubicin on proliferation, invasion and adhesion of SGC7901 cell line, and potential underlying mechanisms. Methods MTT and Transwell experiments were used respectively to investigate the effect of different concentrations of zoledronic acid and doxorubicin on the proliferation, adhesion and invasion of SGC7901. The mRNA levels of MMP2, TIMP2, MMP9, ICAM1 and CD44 were quantified by real time PCR. Results Gastric cell line SGC-7901 were incubated with zoledronic acid for 48 h in different concentration of 10 6, 10- 5 , 10 4,10 3 mol/L, their inhibition rates were 4.98%, 12. 19%, 27.34% and 73.13% separately, which were higher than control group （P〈0.01）, and enhanced along with the dose increasing and the time extension （P〈0. 05）. Gastric cell line SGC-7901 was incubated with zoledronic acid 10 4 tool /L and doxorubicin 0.5 rag/L, respectively, or in combination for 2 h, 4 h, 6 h, and thereafter, the detected adhesion rates were 5.03%, 24.38% and 59.65% in control group, 4.40%, 19.77% and 51.22% in zoledronic acid group, 4.28%, 18.62% and 51.02% in doxorubicin group, 4.02 %, 15.02% and 46.95% in combination group. The adhesion rates were reduced after incubation with different medicament concentration （P〈0.05）. In the study of cell invasion, the cell numbers per high power field were： 105.11±10.43, 98.37 ± 15.75, 96.19± 9.24, 83.02± 19.72 after treatment with zoledronic acid, doxorubicin or their combination at different concentrations. Compared with control, signal medicament had weak effectiveness in invasiveness in SGC-7901 （P〉 0. 05）, whereas in combination group it was significantly decreased （P〈0.05）. Both zoledronic acid and doxorubicin decreased the mRNA expressions of CD44, MMP2, MMP9, ICAM1 while increased TIMP2 mRNA level （P〈0.05 or P〈0.01） versus control. The effect was more evident with combination treatment（P%0.05 or P〈 0.01）, compared with doxorubicin group. Con
出处
《中华老年医学杂志》
CAS
CSCD
北大核心
2012年第8期711-715,共5页
Chinese Journal of Geriatrics
基金
无锡市2011年第十三批科技计划资助项目（CSE01N1114）
关键词
表柔比星
细胞增殖
肿瘤浸润
细胞黏附
胃肿瘤
Epirubicin
Cell proliferation Neoplasm invasveness Cell adhesion Stomach neoplasms
