OncoTargets and Therapy (May 2018)
A new apatinib microcrystal formulation enhances the effect of radiofrequency ablation treatment on hepatocellular carcinoma
Abstract
Hui Xie,1,2 Shengtao Tian,2 Haipeng Yu,1 Xueling Yang,1 Jia Liu,3 Huaming Wang,2 Fan Feng,2 Zhi Guo1 1Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China; 2Department of Interventional Therapy, 302nd Hospital of People’s Liberation Army, Beijing, People’s Republic of China; 3Department of Blood Transfusion, 302nd Hospital of People’s Liberation Army, Beijing, People’s Republic of China Introduction: Radiofrequency ablation (RFA) is the foremost treatment option for advanced hepatocellular carcinoma (HCC), however, rapid and aggressive recurrence of HCC often occurs after RFA due to epithelial–mesenchymal transition process. Although combination of RFA with sorafenib, a molecular targeted agent, could attenuate the recurrence of HCC, application of this molecular targeted agent poses a heavy medical burden and oral administration of sorafenib also brings severe side effects. Materials and methods: In this study, we prepared an apatinib microcrystal formulation (Apa-MS) that sustainably releases apatinib, a novel molecular targeted agent, for advanced HCC treatment. We injected apatinib solution or Apa-MS into subcutaneous HCC tumors. Results: It was found that Apa-MS exhibited slow apatinib release in vivo and in turn inhibited the epithelial–mesenchymal transition of HCC cells for extended time. Moreover, in rodent HCC model, Apa-MS enhanced the antitumor effect of RFA treatment. Conclusion: Based on these results, we conclude that Apa-MS, a slow releasing system of apatinib, allows apatinib to remain effective in tumor tissues for a long time and could enhance the antitumor effect of RFA on HCC. Keywords: apatinib microcrystals, radiofrequency ablation, sustained releasing behavior, long-acting efficiency, epithelial–mesenchymal transition, interventional therapy
