[Effects of Akt2-siRNA on chemotherapeutic sensitivity and drug resistance in human lung cancer cells].

Objective To explore the effects of oncogene protein v-akt-siRNA on the sensitivity of human lung cancer cell line NCI-H446 to cisplatin and drug resistance proteins in human lung cancer cells.Methods The small interfering siRNA expression vector targeting Akt2 gene (siAkt2) was constructed. And the NCI-H446 cells were transfected with negative control vector or siRNA vector. The expressions of Akt2-mRNA and lung resistance-related protein (LRP) and P-glycoprotein (P-gp) were detected by reverse transcription-polymerase chain reaction and immunocytochemistry respectively. NCI-H446 and transfected cells were treated by cisplatin for 24 h. The cell proliferation was measured by 3- (4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay and cell apoptotic rate detected by flow cytometry.Results Akt2-mRNA decreased significantly in the transfected NCI-H446 cells versus the non-transfection group. And the expressions of LRP and P-gp proteins decreased significantly in the transfection group versus the control group (P<0.01). The cell proliferation rate decreased from (60.2±2.8)% to (34.7±2.6)% (P<0.01). The cell apoptotic rate increased from (19.3±1.6)% to (38.8±1.2)% after a therapy of cisplatin (P<0.01).Conclusion The siRNA targeting Akt2 can decrease the Akt2 expression, increase the chemotherapeutic sensitivity to cisplatin and partially reverse the cisplatin resistance of NCI-H446. The mechanism may be through the lowered expressions of LRP and P-gp. Key words: Lung neoplasms; RNA, small interfering; Oncogene protein v-akt; Cisplatin; Drug resistance, neoplasmic