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Tuberostemonine reverses multidrug resistance in chronic myelogenous leukemia cells K562/ADR
Yu Jia Wang1, Huan Dong Zhao2,3, Cai Feng Zhu4
1Tongren Hospital, School of Medicine, Shanghai JiaoTong University, 1111 Xianxia Road, Changning District, Shanghai 200336, China.
Abstract:
Objective: To investigate the reversal effect of tuberostemonine on MDR in myelogenous leukemia cells K562/ADR. Methods: Human myelogenous leukemia cells K562 and their adriamycin-resistance cells K562/ADR were used. The growth curve of cells treated by tuberostemonine and the Non-toxic concentration of tuberostemonine were determined by MTT, Cell apoptosis was determined by MTT and flow cytometry. The expression of MDR1, Survivin and Livin was detected by RT-PCR. The activity of P-gp was detected by flow cytometry. Western blot was used to detect the expression of NF-κB and Survivin. Results: The effect of tuberostemonine on K562/ADR showed a dose-dependence, and 350μg/mL and 500μg/mL of tuberostemonine could inhibit the expression of MDR1 (P<0.05). While no function difference of P-gp was detected. With the increased concentration of tuberostemonine, the inhibitory effect were enhanced to the expression of NF-κB. Tuberostemonine combined with adriamycin could time-dependently inhibit the cell proliferation (P<0.05) and obviously promoted the cell apoptosis (P<0.05). Also the tuberostemonine could inhibit the expression of Survivin. Conclusion: There are no direct relations between tuberostemonine and P-gp, but tuberostemonine could reverse the multidrug resistance of K562/ADR via down-regulating the expression of Nf-κB and inhibiting th1e expression of Survivin.
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