A new apatinib microcrystal formulation enhances the effect of radiofrequency ablation treatment on hepatocellular carcinoma

Abstract

IntroductionRadiofrequency 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 methodsIn 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.ResultsIt 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.ConclusionBased 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.

MicroRNA-645 targets urokinase plasminogen activator and decreases the invasive growth of MDA-MB-231 triple-negative breast cancer cells

“… 44 , 45 After four to eight weeks of growth, the mice were harvested. The liver organs with nodules formed by the MDA-MB-231 cells were collected for Masson staining, following the methods described by Shao et al and Xie et al 46 , 47 The photographs of the Masson staining were quantitatively analyzed to determine the relative invasive growth of the MDA-MB-231 cells using the ImageJ software, following the methods descripted by Shao et al and Xie et al 46 – 48 The thickness of the nodules or liver organs was determined, and the relative invasive growth of the MDA-MB-231 cells in the nude mice’s livers (the nodule thickness relative to that of the liver organ) was calculated as follows: (the nodule thickness of the control group)/(the liver organ thickness of the control group) × 100% or (the nodule thickness of the administration group)/(the liver organ thickness of the administration group) × 100%. The inhibition rate of each group was calculated as follows: ([the control group relative invasive growth) - (the administration group relative invasive growth])/(the control group relative invasive growth) × 100%.…”

MicroRNA-3163 targets ADAM-17 and enhances the sensitivity of hepatocellular carcinoma cells to molecular targeted agents

“…These agents (4 mg each) were dissolved in a mixture of dimethyl sulfoxide (15 μl), polyethylene glycol 400 (60 μl), and Tween80 (40 μl). Physiological saline was carefully added to the solution (agents dissolved in organic solvent) to a total volume of 20 ml 36,37 . Therefore, the concentration of agents was 0.2 mg/ml.…”

MicroRNA-140-3p enhances the sensitivity of hepatocellular carcinoma cells to sorafenib by targeting pregnenolone X receptor

“…MHCC97-H cells, which were transfected with plasmids, were injected into the nude mice to form subcutaneous tumors or into the liver organs via hepatic portal vein injection. 24 Five days after injection, the nude mice were orally administrated 2 mg/kg sorafenib treatment every 2 days. After 10 × treatments for 21 days, the mice were collected.…”

“… 21 , 22 For the intrahepatic growth model, mice were harvested and the liver organs with nodules formed by MHCC97-H were collected for taking photographs. Photographs were quantitatively analyzed to determine the total amount of nodules by ImageJ software following the methods described by Xie et al 24 The inhibition rate of each group was calculated as [control group relative nodule area (percentages of nodules to total area of liver organs, %) - administration group relative nodule area]/control group relative nodule area × 100%.…”