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

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.

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.

• 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)

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

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)