Inhibition of FoxM1 sensitizes leukemia K562 cells to homoharringtonine |
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Authors: | CHEN Jin ZHOU Min-ran SUN Ting QIN Xue-mei CHEN Zhong-min CHEN Chun-yan YU Yuan |
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Affiliation: | 1. Anhui Medical College, Hefei 230601, China;2. Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, China;3. School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China |
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Abstract: | AIM: To study whether inhibition of forkhead box protein M1(FoxM1) sensitizes leukemia K562 cells to homoharringtonine (HHT). METHODS: K562 cells were incubated with HHT at different concentrations (0μmol/L, 0.015μmol/L, 0.030μmol/L and 0.045μmol/L) for different time (0 h, 24 h, 48 h and 72 h). The mRNA and protein levels of FoxM1 were detected by real-time PCR and Western blot. FoxM1 siRNA was transfected into K562 cells with 0.015μmol/L HHT after 6 h. After 72 h incubation, the cell proliferation was detected by cell counting and soft agar assay, and the proportion of apoptotic K562 cells was determined by flow cytometry. The expression of c-Myc and Sp1 were detected by real-time PCR and Western blot. RESULTS: FoxM1 expression was reduced time-dependently and dose-dependently, suggesting that HHT mediated the downregulation of FoxM1 in K562 cells. In K562 cells, treatment with FoxM1 siRNA and HHT inhibited the cell proliferation and promoted the apoptosis significantly. Therefore, inhibition of FoxM1 sensitized leukemia K562 cells to HHT. The expression of c-Myc and Sp1 was positively regulated by FoxM1. CONCLUSION: HHT inhibits Forkhead box protein M1 expression in K562 cells. Inhibition of FoxM1 sensitizes K562 cells to HHT. |
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Keywords: | Homoharringtonine Forkhead box protein M1 K562 cells Drug sensitivity |
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