Chlorogenic-induced inhibition of non-small cancer cells occurs through regulation of histone deacetylase 6.

Chlorogenic acid (CGA), an ester with various pharmacological effects, is important in cancer therapy. However, the specific antitumor mechanism of CGA is not entirely clear, especially with respect to its suppression of non-small cell lung cancer (NSCLC). The present study was carried out to assess the effect of CGA on NSCLC, and the mechanism involved. Cell viability assay and colony formation assay revealed that CGA blocked the proliferative capacity of NSCLC cells in vitro. Results from the migration assay suggested that CGA also inhibited the migration of A549 cells. Other assays further revealed that CGA strongly and selectively inhibited histone deacetylase 6 (HDAC6) activity and suppressed the activity of matrix metalloproteinase-2 (MMP-2) through decreased expression of Ac-NF-κB. Tumorigenicity assay showed that CGA also inhibited the proliferation and metabolism of NSCLC in vivo. These results indicate that CGA significantly suppresses the proliferation of NSCLC by regulating the activity of histone deacetylase 6.

Relationship between Lp-PLA_2 and vulnerable atherosclerotic plaque in rabbits / 中国病理生理杂志

AIM: To explore the expressive role of lipoprotein-associated phospholipase A_2, high sensitive C-reactive protein and matrix metalloproteinase-9 in vulnerable atherosclerotic plaques in a rabbit model. METHODS: Forty eight New Zealand white male rabbits were randomly divided into 4 groups (12 rabbits each): control group, stable plaque group, p53 group, and p53+drug group. Rabbits in control group were fed with a regular diet and underwent sham operation. Rabbits in stable plaque group, p53 group and p53+drug group underwent balloon induced arterial wall injury and then were fed on a diet with 1% cholesterol. The animals were all fed for 3 months, then the rabbits in p53 group and p53+drug group underwent Ad5-CMV p53 transfection at 10th week. Before killed, the animals in p53+drug group underwent pharmacological triggering with Russell's viper venom (RVV) and histamine to induce the rupture of the atherosclerotic plaques. At the 1st day and before sacrifice, the serum was collected for measuring Lp-PLA_2, hs-CRP, MMP-9, HDL, LDL and VLDL. The expressions of Lp-PLA_2, hs-CRP and MMP-9 in tissues were determined by the methods of hybridization and immunohistochemistry. RESULTS: At the end of 12th week, the serum and tissue levels of Lp-PLA_2 and MMP-9 in stable plaque group, p53 group and p53+drug group were significant different from those in control group and in each group at the first day (P<0.05). The serum levels of Lp-PLA_2 and hs-CRP in p53 group and p53+drug group were significantly higher than those in control group and stable group (P<0.05). The serum levels of Lp-PLA_2, hs-CRP and MMP-9 were all significantly different between p53 group and p53+drug group (P<0.05). At the end of 12th week, pathological results showed that 4 groups were normal artery, stable plaque, vulnerable plaque and rupture plaque, respectively. The fabric cap was thicker in plaque groups than that in normal group (P<0.05). The rupture and formation of thrombus were more significant in p53+drug group than those in p53 group. The serum level of Lp-PLA_2 had negative interrelated relationship with fabric cap in plaque groups (r=-0.710, P<0.01), and hs-CRP, MMP-9 had no interrelated relationships with fabric cap in plaque groups. CONCLUSION: Base on the successful establishment of the atherosclerotic plaque animal model, serum Lp-PLA_2 shows better interrelated relationships to plaques stability. Combination with hs-CRP and MMP-9, we can exactly evaluate the nature of plaques.

The correlation of human serum Lp-PLA2 and hs-CRP and stability of coronary atherosclerotic plaques / 中华内科杂志

w biomarker to predict the presence of vulnerable plaque.