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[Effects of Akt2-siRNA on chemotherapeutic sensitivity and drug resistance in human lung cancer cells].
- Source :
-
Zhonghua yi xue za zhi [Zhonghua Yi Xue Za Zhi] 2011 Aug 16; Vol. 91 (30), pp. 2139-42. - Publication Year :
- 2011
-
Abstract
- 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.<br />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-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay and cell apoptotic rate detected by flow cytometry.<br />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).<br />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.
- Subjects :
- ATP Binding Cassette Transporter, Subfamily B metabolism
Antineoplastic Agents pharmacology
Cell Line, Tumor
Cisplatin pharmacology
Humans
Lung Neoplasms drug therapy
Proto-Oncogene Proteins c-akt genetics
RNA, Messenger genetics
Transfection
Vault Ribonucleoprotein Particles metabolism
Drug Resistance, Neoplasm drug effects
Proto-Oncogene Proteins c-akt metabolism
RNA, Small Interfering pharmacology
Subjects
Details
- Language :
- Chinese
- ISSN :
- 0376-2491
- Volume :
- 91
- Issue :
- 30
- Database :
- MEDLINE
- Journal :
- Zhonghua yi xue za zhi
- Publication Type :
- Academic Journal
- Accession number :
- 22093993