Effect of cetuximab combined with adriamycin on proliferation and apoptosis of triple negative breast cancer cells
10.3969/j.issn.1001-1978.2015.12.021
- VernacularTitle:西妥昔联合阿霉素对三阴乳腺癌细胞增殖与凋亡的影响
- Author:
Xiu WANG
;
Jianchun LI
;
Jingjing ZHANG
;
Surong ZHAO
;
Hao LIU
- Publication Type:Journal Article
- Keywords:
triple negative breast cancer;
drug combi-nation;
cetuximab;
adriamycin;
mitochondrial mem-brane potential;
apoptosis
- From:
Chinese Pharmacological Bulletin
2015;(12):1735-1740
- CountryChina
- Language:Chinese
-
Abstract:
Aim To detect the effects of cetuximab combined with adriamycin on the proliferation and ap-optosis of triple-negative breast cancer cells.Methods Cell viability was evaluated by MTT assay.The cell apoptosis was analyzed by flow cytometry with propidi-um iodide staining.JC-1 staining was used to deter-mine mitochondrial membrane potential.The expres-sions of glucose regulated protein78 (GRP-78),Bcl-2 and Caspase-3 were measured with Western blot.Re-sults MTT assay showed that cetuximab had inhibi-tion effect on the breast cancer cell MDA-MB-231 growth,and the effect was related to concentration of drug.The inhibition effect of adriamycin on MDA-MB-231 had remarkabe relationship with time and concen-tration.When combined with each other,they could re-markably increase inhibition effect.The viability of cells in combination group for 1 2 h,24 h,48 h,sig-nificantly lower than that in cetuximab or adriamycin group (P <0.05 or P <0.01 ).Apoptosis results showed that cell apoptosis was significantly increased when cetuximab combined with adriamycin,reached (43.93 ±3.59)% for 24 h,had remarkably statistical significance compared to cetuximab or adriamycin
group (P <0.01 ).JC-1 staining indicated that cetux-imab or adriamycin could reduce the mitochondrial membrane potential,but the reduction effect was more remarkable in the combination group.Western blot re-vealed that cetuximab could reduce the expression of GRP-78 and Bcl-2,and increased the expression of Caspase-3 and its activity.The expressions of Bcl-2, Caspase-3 had no significant change in adriamycin group,but GRP-78 was increased.In combination group,the expression of GRP-78 and Bcl-2 was signifi-cantly decreased,but Caspase-3 was increased nota-blely compared to adriamycin group.Conclusions The combination of cetuximab and adriamycin enhances the inhibition effect on the triple-negative breast cancer MDA-MB-231 cells,and increases cell apoptosis.The mechanism may be that cetuximab reduces the endo-plasmic reticulum stress level,then activates the mito-chondrial pathways by decreasing the expression of Bcl-2,reducing the mitochondrial membrane potential,and promoting cell apoptosis.
