Article Abstract

Antineoplastic effects of Endostar combined with combretastatin A4 phosphate in vitro

Authors: Xianhua Fu, Yin Duan, Hongdan Shen, Yong Zou, Chi Pan, Demin Lu, Jianjin Huang, Jun Li, Suzhan Zhang


Background: Endostar is an anti-angiogenesis agent with a favorable toxicological profile. Previous studies demonstrated that the combination of Endostar and combretastatin A4 phosphate (CA4P) had synergy in the antitumor effect in an osteosarcoma xenograft. The present study addressed whether this combination could possess a strong anti-cancer activity in vitro.
Methods: CA4P and/or Endostar were assessed pharmacological properties on K562, K562/ADR, MNNG/HOS, MCF-7, T-47D, HT29 cells. Cell inhibition rate of CA4P and/or Endostar was measured using MTT assay. Cell cycle distribution was analyzed by flow cytometry. Apoptosis was assessed using annexin-V/PI assays, whereas mRNA expression levels of caspase 3, caspase 9, caspase 8, Bax, and Bcl-2 were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR).
Results: Among six cell lines, MNNG/HOS cells and HT29 cells are chosen to further study. The IC50 values obtained with the combination of Endostar and CA4P were the lowest. Further analyses clarified that in comparison to CA4P alone or Endostar alone, Endostar + CA4P significantly increased G2/M-phase blockage, apoptosis and necrosis, up-regulation caspase 3, caspase 8, caspase 9 and Bax mRNA and down-regulation of Bcl-2 mRNA.
Conclusions: Our results indicated that the combination of Endostar and CA4P had the effect of synergistic cytotoxicity and provide a useful insight into combined effects of Endostar and other traditional microtubule-targeting drugs.