Effects of Sensitized Sorafenib with a Paeoniflorin and Geniposide Mixture on Liver Cancer via the NF-κB-HIF-2α-SerpinB3 Pathway.

Purpose: This study focused on determining the anticancer effect of paeoniflorin and geniposide mixture (PFGS) combined with sorafenib (Sor) in hepatocellular carcinoma (HCC) and, in particular, whether PFGS increases the antitumor effect of Sor by modulating the NF-κB/HIF-2α/SerpinB3 pathway. Methods: The H22 hepatoma tumor-bearing mouse model was treated with PFGS, Sor, and a combination of the two drugs for 12 days. The effects of PFGS combined with Sor on tumor growth and apoptosis and the expression of NF-κB, HIF-2α, and SerpinB3 in tumor tissue were assessed. In addition, Sor-resistant hepatoma cells were treated with PFGS, Sor, and the combination of the two drugs in vitro. The effects of PFGS combined with Sor on cell proliferation and invasion and the protein expression of NF-κB p65, HIF-2α, and SerpinB3 were investigated. Results: PFGS combined with Sor treatment synergistically inhibited tumor growth in HCC tumor-bearing mice. Immunostaining showed that PFGS combined with Sor treatment significantly decreased the expression of Ki-67 and obviously induced apoptosis in the tumor compared with a single treatment. Similarly, PFGS combined with Sor treatment significantly downregulated the expression of NF-κB, HIF-2α, and SerpinB3 in the tumor compared with a single treatment. Additionally, PFGS combined with Sor markedly inhibited cell proliferation and invasion and activation of the NF-κB/HIF-2α/SerpinB3 pathway in Sor-resistant hepatoma cells compared with a single treatment. Conclusion: Our study demonstrated that PFGS synergistically increased the antiliver cancer effects of Sor by lowering activation of the NF-κB/HIF-2α/SerpinB3 pathway. These findings provided a scientific foundation for clinical studies using PFGS and Sor to treat liver cancer.

[Impact of acute glucose and fat loading on endothelium dependent vasodilation in patients with essential hypertension].

OBJECTIVE: To explore the influence of acute glucose and fat loading on endothelium dependent flow-mediated vasodilation (FMD) in patients with essential hypertension (EH). METHODS: Patients with EH were randomly divided into three groups: oral glucose loading alone (n = 26), oral standardized fat loading alone (n = 38), combined glucose and fat loading (n = 34). FMD of the brachial artery was assessed by high resolution ultrasound technique respectively. RESULTS: (1) Compared to control group, postprandial abnormal serum triglyceride metabolism was evidenced and FMD was significantly reduced and the lowest FMD occurred at 4 hours and returned to the baseline level at 8 hours post fat loading alone in EH patients. (2) GS-AUC and 1 hour glucose were significantly higher in EH patients than in controls (all P < 0.05), FMD was also significant decreased (-31.4%) at 1 hour and returned to baseline level at 2 hours post oral glucose loading. (3) After combined glucose and fat loading, FMD at 1 hour (5.45 ± 1.93 vs. 9.46 ± 3.33, P < 0.05) was significantly lower than that in glucose loading alone and FMD at 4 hours (7.98 ± 1.64 vs. 9.66 ± 2.26, P < 0.05), was also lower than that in fat loading alone in EH patients. (4) FMD was negatively correlated with SBP, GS-AUC, DBP, TG-AUC (γ = -0.46, -0.44, -0.41, -0.38, respectively, all P < 0.05). CONCLUSION: Combined glucose and fat loading additively reduced FMD in hypertensive patients.