The biological effects of zoledronic acid in combination with doxorubicin on SGC-7901 cell line of gastric cancer
10.3760/cma.j.issn.0254-9026.2012.08.023
- VernacularTitle:唑来膦酸联合阿霉素对胃癌细胞株SGC-7901的生物学作用
- Author:
Hao YU
;
Yan ZHANG
;
Ying ZHANG
;
Dong HUA
- Publication Type:Journal Article
- Keywords:
Epirubicin;
Cell proliferation;
Neoplasm invasveness;
Cell adhesion;
Stomach neoplasms
- From:
Chinese Journal of Geriatrics
2012;31(8):711-715
- CountryChina
- Language:Chinese
-
Abstract:
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 mol /L and doxorubicin 0.5 mg/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<0.05or P<0.01) versus control.The effect was more evident with combination treatment(P<0.05 or P<0.01),compared with doxorubicin group. Conclusions Both zoledronic acid and doxorubicin can inhibit the proliferation,adhesion and invasion of SGC7901. Combination treatment has additive effect.It may be related to the down-regulation of mRNA of ICAM1,MMP2,MMP9,CD44 and up-regulation of mRNA of TIMP2.