Silence of Spermidine/Spermine N¹-Acetyltransferase Expression by SiRNA Decreases Sensitivity of Human A549 Lung Cancer Line to Antitumor Polyamine Analogue CPENSpm

OBJECTIVE To investigate the effect of expressive silence of spermidine/spermine N1-acetyltransferase (SSAT) on the actitumor activity of polyamine analogue CPENSpm (N1-cyclopropylmethyl-N11-ethylnorspermine). METHODS SiRNA technique was used to silence expression of SSAT gene in human lung cancer line A549. QT-RT-PCR was performed to assay the expression level of SSAT genes. The cell proliferation was detected by MTT assay. The apoptosis of A549 cells were evaluated by DNA fragmentation and Sub-G1/flow cytometry assay. RESULTS The A549 cell line in which SSAT expression was silenced successfully was obtained. Treating A549 control cells by 10 μmol·L^-1 CPENSpm for 24 hours resulted in a 23-folds up-regulation of SSAT expression in mRNA level, but no this effect was observed in SSAT-silence cells. MTT assay demonstrated that SSAT-silence decreased the sensitivity of A549 cells to CPENSpm exposure (0-20 μmol·L^-1). DNA fragmentation and sub-G1 assay proved the ability of CPENSpm to induce apoptosis only in the control A549 cells but not in the SSAT-silence cell line. CONCLUSION Up-regulation of SSAT by CPENSpm is possibly one of the molecular bases for its antitumor activity.