The effect of antisense oligodeoxynucleotides targeting Aurora A kinase on cell proliferation and chemosensitivity to paclitaxel in human lung cancer cell line A549

21147 Background: Aurora kinases representing a family of evolutionarily conserved mitotic serine/threonine kinases have been found elevated in lung andenocarcinoma cell line A549. It is suggested that the overexpression of Aurora A contributes to the carcinogenesis, chromosomal instability (CIN), and de-differentiation of lung cancers. To address its possibility as a therapeutic target for lung cancer, we employed the antisense oligodeoxynucleotide (ASODN) technique to inhibit Aurora A expression and investegate its effect on tumor growth and cell cycle of A549, as well as the chemosensitivity of paclitaxel. Methods: Aurora A ASODN was synthesized and transfected into A549 cells by lipofectAMINE 2000.Aurora A mRNA and protein expression were examined by reverse transcription -polymerase chain reaction (RT-PCR) and Western blot respectively.Cell cycle distribution was observed by flow cytometer.MTT assay was used to evaluate cell inhibition ratio before and after transfection. Results: The proliferation of the A549 cells was inhibited by Aurora A ASODN dose and time dependently. It was also observed that the IC50 of A549 cells after 48 hours’ treatment of ASODN was about 300nmol/L and under such circumstances, the Aurora A mRNA and protein expression significantly decreased (P<0.05), along with the induction of accumulation of cells in S phase and the G2-M transition. Furhermore, cell inhibition ratio of the combination of Aurora A ASODN and paclitaxel was higher significantly than paclitaxel(P<0.05) or Aurora A ASODN alone (P<0.05). Conclusions: Inhibition of Aurora A expression can results in the suppression of cell growth and chemosensitizing activity to paclitaxel in human lung cancer cell line A549. No significant financial relationships to disclose.