In vitro and in vivo antitumor activity of scutebarbatine A on human lung carcinoma A549 cell lines.

During our systematic study on the anticancer activities of Scutellaria barbata, scutebarbatine A (SBT-A), one of the major alkaloids in S. barbata, was found to have antitumor effects on A549 cells. Thus, we designed the present study to investigate in detail the antitumor effects of SBT-A. The cytotoxic effect of SBT-A on A549 in vitro were determined by an MTT assay and evaluated by IC50 values. Furthermore, results of Hoechst 33258 and Annexin V/PI staining assays demonstrated that SBT-A had significant antitumor effects on A549 cells via apoptosis, in a concentration-dependent manner. What's more, the mechanism was explored by western blotting, and our study revealed that SBT-A can up-regulate the expressions of cytochrome c, caspase-3 and 9, and down-regulate the levels of Bcl-2 in A549 cells. Finally, the antitumor effects of SBT-A were evaluated in vivo by using transplanted tumor nude mice, and the results confirmed that SBT-A has a notable antitumor effect on A549 cancer via mitochondria-mediated apoptosis. Collectively, our results demonstrated that SBT-A showed significant antitumor effects on A549 cells in vivo and in vitro via mitochondria-mediated apoptosis by up-regulating expressions of caspase-3 and 9, and down-regulating Bcl-2.

Meta-analysis of the efficacy of sorafenib for hepatocellular carcinoma.

PURPOSE: By carrying out a meta-analysis of randomized controlled trials that compared sorafenib or combined chemotherapy with placebo or combined chemotherapy, the effectiveness of sorafenib in hepatocellular carcinoma was evaluated in the present study, which also provided clinical practice guidelines of evidence-based-medicine. METHODS: We reviewed PubMed citations concerning sorafenib treating hepatocellular carcinoma in randomized controlled trials from Jan 2000 to July 2012. All the literature was extracted by Cochrane systematic reviews and underwent meta-analysis with RewMan 5.0 software. RESULTS: Finally, four papers documenting randomized controlled studies were included. Compared with controls, sorafenib was shown to significantly increase overall survival (OS), time to progression (TTP), and disease control rates (DCR), but not the time to symptom progression (TTSP) in hepatocellular carcinoma patients. The incidence of grade-III/IV adverse reactions, including hand- foot-skin reactions, diarrhea, hypertension and skin rash or desquamation, in sorafenib treatment group was higher than that in controls. However, there was no significant difference in the incidence of hypodynamia between the two groups. CONCLUSIONS: Sorafenib exerts significant curative effects in hepatocellular carcinoma.

[Effects of different intraabdominal pressure of carbon dioxide pneumoperitoneum on hemorrheology and microcirculation in rabbits].

OBJECTIVE: To study effects of different intraabdominal pressure of carbon dioxide (Cq2) pneumoperitoneum on hemorrheology and microcirculation in rabbits. METHODS: Eighteen female healthy rabbits weighing 2.2 kg to 3.5 kg were randomly divided into three groups equally based on pneumoperitoneum pressure: 0 mmHg group (group I),10 mmHg group (group II) and 15 mmHg (group III). Each group received 1 h pneumoperitoneum under different pressure. Blood samples were taken at 5 min before CO2 pneumoperitoneum, at 30 and 60 min after pneumoperitoneum for the measurements of indexes of hemorrheology. Hemodynamics including heart rate (HR), mean arterial pressure (MAP) and the volume and velocity of the microcirculation of auricle were continuously monitored, such indexes were recorded at the related time. RESULTS: Afer pneumoperitoneum at 30 and 60 min, compared with group I, HR, MAP, the whole blood viscosity, the aggregation and rigid indexes of RBC were significantly raised in group II (P < 0.05), the deformability indexes of RBC, the volume and velocity of the microcirculation were markedly decreased (P < 0.05). Even more significant changes were observed in group III (P < 0.01). The plasma viscosity and the hematocrit changed little. CONCLUSION: After CO2 pneumoperitoneum, hemorrheology is decreased; Although HR, MAP are raised, the volume and velocity of the microcirculation are decreased.

Hepatic injury induced by carbon dioxide pneumoperitoneum in experimental rats.

AIM: To observe the hepatic injury induced by carbon dioxide pneumoperitoneum in rats and to explore its potential mechanism. METHODS: Thirty healthy male SD rats were randomly divided into control group (n = 10), 0 h experimental group (n = 10) and 1 h experimental group (n = 10) after sham operation with carbon dioxide pneumoperitoneum. Histological changes in liver tissue were observed with hematoxylin-eosin staining. Liver function was assayed with an automatic biochemical analyzer. Concentration of malonyldialdehyde (MDA) and activity of superoxide dismutase (SOD) were assayed by colorimetry. Activity of adenine nucleotide translocator in liver tissue was detected with the atractyloside-inhibitor stop technique. Expression of hypoxia inducible factor-1 (HIF-1) mRNA in liver tissue was detected with in situ hybridization. RESULTS: Carbon dioxide pneumoperitoneum for 60 min could induce liver injury in rats. Alanine aminotransferase and aspartate aminotransferase were 95.7 +/- 7.8 U/L and 86.8 +/- 6.9 U/L in 0 h experimental group, and 101.4 +/- 9.3 U/L and 106.6 +/- 8.7 U/L in 1 h experimental group. However, no significant difference was found in total billirubin, albumin, and pre-albumin in the three groups. In 0 h experimental group, the concentration of MDA was 9.83 +/- 2.53 micromol/g in liver homogenate and 7.64 +/- 2.19 micromol/g in serum respectively, the activity of SOD was 67.58 +/- 9.75 nu/mg in liver and 64.47 +/- 10.23 nu/mg in serum respectively. In 1 h experimental group, the concentration of MDA was 16.57 +/- 3.45 micromol/g in liver tissue and 12.49 +/- 4.21 micromol/g in serum respectively, the activity of SOD was 54.29 +/- 7.96 nu/mg in liver tissue and 56.31 +/- 9.85 nu/mg in serum, respectively. The activity of ANT in liver tissue was 9.52 +/- 1.56 in control group, 6.37 +/- 1.33 in 0 h experimental group and 7.28 +/- 1.45 (10(-9) mol/min per gram protein) in 1 h experimental group, respectively. The expression of HIF-1 mRNA in liver tissue was not detected in control group, and its optical density difference value was 6.14 +/- 1.03 in 0 h experimental group and 9.51 +/- 1.74 in 1 h experimental group, respectively. CONCLUSION: Carbon dioxide pneumoperitoneum during the sham operation can induce hepatic injury in rats. The probable mechanisms of liver injury include anoxia, ischemia reperfusion and oxidative stress. Liver injury should be avoided during clinical laparoscopic operation with carbon dioxide pneumoperitoneum.