PS02.206: THE SYNERGISTIC ANTITUMOR EFFECT OF APATINIB COMBINED WITH CYTOTOXIC DRUGS ON ESOPHAGEAL CANCER

Abstract

Abstract Background Esophageal cancer is one of the most common malignancies in the digestive system in the world. It is difficult to acquire satisfactory effect through chemotherapy which is an essential method to advanced esophageal cancer. Apatinib, a highly selective inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), inhibits the angiogenesis of tumors. Methods The mRNA and protein expression of VEGFR-2 in esophageal cancer cell lines (Eca9706, Eca109, KYSE450, KYSE70) were detected by qRT-PCR and western blot assay. These cell lines were treated with apatinib combined with cytotoxic drugs: cisplatin, paclitaxel, or 5-Fu respectively. Cell proliferation was then measured using CCK-8; cell cycle distribution and apoptosis were analyzed by flow cytometry; cell migration and invasion were evaluated by wound healing and transwell assays. Esophageal cancer xenografts model was established and used to evaluate the the antitumor effects of combination of apatinib and cytotoxic drugs in vivo. Results The mRNA and protein expression of VEGFR-2 were higher in Eca109 and Eca9706 cell lines than those in KYSE70 and KYSE450. The proliferation, migration, and invasion ability of esophageal cancer cells treated with apatinib combined with cytotoxic drugs were lower than those untreated cells. Furthermore, the inhibition effects of apatinib with each cytotoxic drug on the proliferation, migration, and invasion of esophageal cancer cells were greater compared with those treated with either apatinib or cytotoxic drug (P < 0.05). The proportion of G0/G1 phase was increased and the effect of arresting cell cycle were enhanced in esophageal cancer cells treated with apatinib and cytotoxic drugs compared with those treated with either apatinib or cytotoxic drug (P < 0.05). The combination of apatinib with each cytotoxic drug demonstrate synergistic promotion effects on the apoptosis of esophageal cancer cells compared with those treated with either apatinib or cytotoxic drug (P < 0.05). The combination of apatinib with each cytotoxic drug displayed synergistic inhibition effects on the growth of esophageal cancer xenografts compared with those treated with either apatinib or cytotoxic drug (P < 0.05). Conclusion The combination of apatinib with cytotoxic drugs had the synergistic antitumor effects on esophageal cancer. Disclosure All authors have declared no conflicts of interest.