RESUMO
Objective To establish a drug-resistance cell line of human glioma with temozolomide ( TMZ) ,investigate its resistance mechanisms, and provide experimental evidence for optimal TMZ therapy. Methods A TMZ-resistant human glioma cell line,U251/TR,was established by stepwise exposure of human parental U251 cells to TMZ. Resistance index and cell viability were accessed by MTT assay. Western-Blot,RT-PCR,immunohistochemistry and immunofluorescence were used to detect MGMT expression for the analysis of resistance mechanism. Results A TMZ-resistant human glioma cell line,U251/TR,was developed after 8 months of stepwise induction with 0. 25-16. 00 μg·mL-1 TMZ. IC50 in U251/TR cells was approximately 7 times higher compared with that in U251 cells (P=0. 00 ). The MGMT expression was significantly increased in U251/TR cells compared with that in parental U251 cells (P=0. 00) . Conclusion A TMZ-resistant human glioma cell line,U251/TR,was established by stepwise exposure of human parental U251 cells to TMZ. The primary mechanism of TMZ resistance is associated with increased activity of MGMT.
RESUMO
Mild Cognitive Impairment(MCI)is a transitional stage during the progress of cognitive Impairment. Through the analysis of the relativity of apolipoprotein E(apoE),apoE genetic polymorphism,phlegm stagnation and blood stasis,hyperlipemia and MCI,we got this conclusion:syndrome of phlegm stagnation and blood stasis is an important underlying pathogenesis of MCI:the syndrome of phlegm stagnation and blood stasis has a close relation to apoFe4 allele,and lipid-metabolism disturbance is a key link to this relation.