Abstract | OBJECTIVE: 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. 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.
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Authors | Qiu-ge Wu, Ting-ting Cao, Zhe Cheng, Jing Wang |
Journal | Zhonghua yi xue za zhi
(Zhonghua Yi Xue Za Zhi)
Vol. 91
Issue 30
Pg. 2139-42
(Aug 16 2011)
ISSN: 0376-2491 [Print] China |
PMID | 22093993
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- ATP Binding Cassette Transporter, Subfamily B
- Antineoplastic Agents
- RNA, Messenger
- RNA, Small Interfering
- Vault Ribonucleoprotein Particles
- major vault protein
- AKT2 protein, human
- Proto-Oncogene Proteins c-akt
- Cisplatin
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Topics |
- ATP Binding Cassette Transporter, Subfamily B
(metabolism)
- Antineoplastic Agents
(pharmacology)
- Cell Line, Tumor
- Cisplatin
(pharmacology)
- Drug Resistance, Neoplasm
(drug effects)
- Humans
- Lung Neoplasms
(drug therapy)
- Proto-Oncogene Proteins c-akt
(genetics, metabolism)
- RNA, Messenger
(genetics)
- RNA, Small Interfering
(pharmacology)
- Transfection
- Vault Ribonucleoprotein Particles
(metabolism)
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