Role of dephosphorylation of FOXO1 on apoptosis induced by wortmannin for non-Hodgkin's lymphoma cells.
The aim of this study was to ascertain the relationship between the phosphorylation of FOXO1 and the apoptosis and the proliferation of lymphoma cells so as to further clarify the cellular biology and pathogenesis of the disease. The lymphoma cells Namalwa and Jurkat were treated with PI3K inhibitor wortmannin or etoposide alone or wortmannin plus etoposide with different schedule. The inhibition rates of lymphoma cell growth were examined by XTT assay. Apoptosis were detected by flow cytometry. The expression of p-Akt, p-FOXO1, FOXO1, bim were determined by western blot analysis. Wortmannin induced apoptosis of Jurkat cells and Namalwa cells and inhibited their survival effectively. The rate of growth inhibition and apoptosis of lymphoma cells induced by wortmannin plus etoposide were higher than those induced by etoposide alone. After treated with wortmannin, phosphorylation of FOXO1 remarkably reduced and bim increased. The dephosphorylation of FOXO1 inhibited proliferation of Jurkat cells and Namalwa cells, promoted their apoptosis and sensitized Non-Hodgkin lymphoma cells to etoposide. Bim activated by FOXO1 promoted cells apoptosis.
Qiong
Zhan
Z
Department of Oncology, Huashan Hospital, Fudan University, 200040, Shanghai, People's Republic of China.
Ruofan
Huang
H
Xiaohua
Liang
L
Xinli
Zhou
Z
Jingwei
Jiang
J
Zhaohui
Chu
C
D000730:Androstadienes / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000494:pharmacology; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects; D000077191:Wortmannin
D000730:Androstadienes; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D005047:Etoposide; D000077191:Wortmannin