%0 Journal Article
%T PPAR-¦Ã Silencing Inhibits the Apoptosis of A549 Cells by Upregulating Bcl-2
%A Jingyu YANG
%J Chinese Journal of Lung Cancer
%D 2013
%I Chinese Anti-Cancer Association; Chinese Antituberculosis Association
%R 10.3779/j.issn.1009-3419.2013.03.02
%X Background and objective Drug resistance is the one of primary causes of death in patients with lung cancer, PPAR-¦Ã could induce the apoptosis and reverse drug resistance. The aim of this study is to investigate the expression of PPAR-¦Ã on cisplatin sensitivity and apoptosis response of human lung cancer cell line A549. Methods Reconstruction of PPAR-¦Ã silencing A549 cells (A549/PPAR-¦Ã(-)) by siRNA. MTT assay was employed to determine the effect of cisplatin on the proliferation of A549/PPAR-¦Ã(-), flow cytometry to determine the effect of cisplatin on the cell apoptosis, Western blot to determine the change of phosphorylation of Akt, caspase-3 and expression of bcl-2/bax. Finally, RT-PCR was employed to determine the transcriptional level of bcl-2. Results Two PPAR-¦Ã silencing A549 cell clones were established successfully, and the expression of PPAR-¦Ã was downregulated significantly as confirmed by RT-PCR and Western blot. After PPAR-¦Ã silencing, the resistance of these two A549 clones to cisplatin was increased by 1.29-fold and 1.60-fold respectively. Flow cytometry showed that the apoptosis rate was decreased, and Western Blot showed that the phosphorylation of Akt and expression of bcl-2/bax were upregulated, caspase-3 was downregulated. Finally, RT-PCR showed that the transcriptional level of bcl-2 was upregulated as well. Conclusion Downregulation of PPAR-¦Ã in A549 cells led to increase of cisplatin resistance. One of the mechanisms was upregulatin of phosphorylation of Akt and expression of bcl-2, which inhibited the apoptosis of cells. The downregulation of PPAR-¦Ã is a possible mechanism that leads to the clinical drug resistance of cancer.
%K PPAR-¦Ã
%K Bcl-2
%K Apoptosis
%K Lung neoplasms
%U http://dx.doi.org/10.3779/j.issn.1009-3419.2013.03.02