ABSTRACT
OBJECTIVE Lapachol is a natural naphthoquinone compound that possesses extensive biological activities. The aim of this study is to investigate the inhibitory effects of lapachol on rat C6 glioma both in vitro and in vivo, as well as the potential mechanisms. METHODS The antitumor effect of lapachol was firstly evaluated in the C6 glioma model in Wistar rats. The effects of lapachol on C6 cell proliferation, apoptosis and DNA damage were detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS)/ phenazinemethosulfate (PMS) assay, hoechst 33358 staining, annexinⅤ-FITC/PI staining, and comet assay. Effects of lapachol on topoisomerase I (TOP I) and topoi?somerase Ⅱ (TOP Ⅱ) activities were detected by TOP Ⅰ and TOP Ⅱ mediated supercoiled pBR322 DNA relaxation assays and molecular docking. TOPⅠ and TOPⅡ expression levels in C6 cells were also determined. RESULTS High dose lapachol showed significant inhibitory effect on the C6 glioma in Wistar rats (P<0.05). It was showed that lapachol could inhibit proliferation, induce apoptosis and DNA damage of C6 cells in dose dependent manners. Lapachol could inhibit the activities of both TOPⅠ and Ⅱ. Lapachol-TOPⅠ showed relatively stronger interaction than that of lapachol-TOPⅡ in molecular docking study. Also, lapachol could inhibit TOPⅡ expression levels, but not TOPⅠ expression levels. CONCLUSION These results showed that lapachol could significantly inhibit C6 glioma both in vivo and in vitro, which might be related with inhibiting TOPⅠ and TOPⅡ activities, as well as TOPⅡ expression.
ABSTRACT
OBJECTIVE@#To investigate the effect of cerebral hemodynamic changes on white matter damage in premature infant with patent ductus arteriosus(PDA).@*METHODS@#A total of 106 premature infants were enrolled in the study, including 35 PDA infants with hemodynamic changes (hsPDA group), 35 PDA infants without hemodynamic changes (non-hsPDA group) and 36 non-PDA infants (control group). Serum level of neuron-specific enolase (NES) was detected and craniocerebral ultrasound examination was performed on d3, d7 and d14 after birth. The correlation between blood flow rate of PDA and gray scale value of lateral ventricle was analyzed.@*RESULTS@#Gray scale values of lateral ventricle and serum levels of NES in hsPDA group were higher than those in control group on d3, d7 and d14 (P0.05). There was a positive correlation between the blood flow rate of PDA and gray scale value of lateral ventricle (r=0.876, P<0.01) in premature infants.@*CONCLUSION@#Patent ductus arteriosus with hemodynamic changes is closely related to white matter damage in premature infants, and early intervention is necessary.