The synergistic effects of Apatinib combined with cytotoxic chemotherapeutic agents on gastric cancer cells and in a fluorescence imaging gastric cancer xenograft model
Received 15 December 2017
Accepted for publication 30 March 2018
Published 24 May 2018 Volume 2018:11 Pages 3047—3057
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Carlos E Vigil
Jiuhuan Feng,1 Shukui Qin2
1Institute of First Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China; 2Oncology Center of PLA, 81 Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
Introduction: Methylsulfonic apatinib (hereinafter referred to as Apatinib) is a small-molecule angiogenesis inhibitor highly and selectively targeted to vascular endothelial growth factor receptor-2. At present, a series of basic and clinical studies have confirmed that Apatinib monotherapy can inhibit the growth of different carcinomas. Our experiment aimed to determine whether there is a synergistic effect between the combination of the traditional cytotoxic chemotherapy drugs paclitaxel (TAX), oxaliplatin (L-OHP), 5-fluorouracil (5-FU), and Apatinib.
Materials and methods: We evaluated the combined effect using cytological experiments and a fluorescence imaging xenograft model. In vitro, the inhibition of cell proliferation increased notably when Apatinib was combined with TAX, L-OHP, and 5-FU. Then, for the mechanistic research, we selected the optimal dose of drugs that also had a synergistic effect. Apatinib combined with the aforementioned drugs, especially the combination of Apatinib and 5-FU, decreased the invasion and migration ability of the cells and increased the apoptosis ratio; expression of the anti-apoptotic protein Bcl-2 significantly decreased, and expression of the pro-apoptotic protein Bax increased. In vivo, when Apatinib was combined with TAX, L-OHP, and 5-FU, the volume of the xenograft model was significantly inhibited, the strength of the green fluorescence was weakened and the microvessel density decreased.
Results: The combination of Apatinib with TAX and 5-FU was synergistic (coefficient of drug interaction <1); the combination effect of Apatinib and L-OHP was only additive, with a shorter associated survival time.
Conclusion: The combination of Apatinib and classical chemotherapy drugs may be an optimal choice for gastric cancer treatment.
Keywords: gastric cancer, Apatinib, chemotherapy, fluorescence imaging
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