ABSTRACT
Aim To further analyze the effects of PTEN/Akt/MDM2 signaling pathway in the harmine (HM)-mediated inhibition of COX-2 expression in gastric cancer cells. Methods PTEN-siRNA, Akt-siR-NA, MDM2-siRNA were constructed and respectively transfected into SGC-7901 and MKN45 cells,and then added or not added HM for 24 h. The expression of PTEN, Akt and phosphorylated Akt ( p-Akt), MDM2 and phosphorylated MDM2 ( p-MDM2), as well as COX-2 expression was detected by Western blot. Results HM increased PTEN expression, but inhibited p-Akt,p-MDM2 and COX-2 expression in SGC-7901 and MKN45 cells. Knockdown of PTEN blocked HM-induced inhibition of Akt and MDM2 phosphorylation, as well as down-regulation of COX-2 expression. Knockdown of Akt and treatment with HM synergisti-cally inhibited p-MDM2 and COX-2 expression. Knockdown of MDM2 and treatment with HM synergis-tically inhibited COX-2 protein expression. Conclusions HM down-regulates the expression of COX-2 protein in gastric cancer cells via PTEN/Akt/MDM2 signaling pathway.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the genotype distribution of hemoglobinopathy in Chinese Jiangsu population.</p><p><b>METHOD</b>A total of 4115 samples were screened for hemaglobinopathy by using MCV combined with erythrocyte fragility tests and HPLC. Thalassemia genotypes were identified by Gap-PCR and Recerse Dot blot. PCR-DNA sequencing and PCR-elecrophoresis were used as supplement of PCR-RBD and for identifying the mutants of globin gene of abnormal hemoglobin.</p><p><b>RESULTS</b>The positive screening rate was 6.10% (251/4115) in Chinese Jiangsu population, 232 cases received thalassemia genotype diagnosis and from them 195 people were positive. In all positive ones, α-thalassemia, β-thalassemia, α-thalassemia combined with β-thalassemia, SEA-HPFH and SEA-HPFH combined with β-thalassemia were found respectively to be 31.28% (61/232), 66.15% (129/232), 1.54% (3/232), 0.43% (1/232) and 0.43% (1/232) of patients. The majority genotype of α-thalassemia was - - (SEA) and IVS-II-654 was the main genotype of β-thalassemia, 11 cases of abnormal hemoglobin were found, including 3 cases of Hb E, 1 Hb Kenitra, 1 Hb Seattle, 1 Hb Saitama, 1 Hb Bushwick, 1 Hb Koln and 1 Hb M-Milwaukee-2.</p><p><b>CONCLUSION</b>The main hemoglobinpathy is thalassemia in Chinese Jiangsu province and the HPLC play an important role in screening hemoglobinpathy. There is reference value of this study for genetic counseling and prenatal diagnosis.</p>