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  • Title: [Inhibition of activation of nuclear factor-KappaBeta enhances apoptosis induced by chemotherapeutic drugs in P388 cell line].
    Author: Shi J, Xu X, Li L, Zhang Z, Cheng W, Niu Y, Ge J.
    Journal: Zhonghua Yi Xue Za Zhi; 2002 Aug 10; 82(15):1050-3. PubMed ID: 12194797.
    Abstract:
    OBJECTIVE: To explore the effects of glucocorticoid on apoptosis of mouse acute lymphocytic leukemia P388 cells and activation of nuclear factor-Kappa-gene binding (NF-KappaBeta) in P388 cells induced by chemotherapeutic drugs. METHODS: Mouse acute lymphcytic leukemia P388 cells were cultured. with 1.0 micro mol/L thasone (DXM) hours. Then Cytosine arabinoside Ara-C), cyclophosphamide Cy , and etoposide VP16 , of different concentrations were added into the cultures. Twelve hours later, the apoptosis induced by these drugs in P388 cells was analysed by TdT-mediated kappa-dUTP nick and end labeling (Tunel) and DNA electrophoresis. P388 cells in the exponential growth stage (1 x 10(6)/ml) were cultured with DXM (1.0 micro mol/L) for 2 hours. Then Ara-C, Cy, DXM, and VP16 were added into the culture. Three hours later electrophoretic mobility shift assay (EMSA) was conducted to determine the DNA binding activation of NF-KappaBeta. RESULTS: The highest apoptosis rates of P388 cells induced by Ara-C, Cy, and VP-16, were 48.3% +/- 2.6%, 21.4% +/- 6.8%, and 38.1% +/- 3.8%, respectively. The apoptosis rate of P388 cells induced by Ara-C + DXM was 69.6% +/- 7.7%, 44% higher than that induced by only Ara-C (48.3% +/- 2.6%); the apoptosis rate of P388 cells induced by Cy + DXM was 35.6% +/- 6.8%, 89% higher than that induced by only Cy (21.4% +/- 6.8%); and the apoptosis rate of P388 cells induced by VP-16 + DXM was 71.9% +/- 9.9%, 66% higher than that induced by only VP-16 (38.1% +/- 3.8%) (all P < 0.01). Ara-C, Cy, and VP-16 significantly increased the activation of NF-KappaBeta in P388 cells. Pre-processing of 1.0 micro mol/L DXM suppressed the activation of NF-KappaBeta in P388 cells induced by Ara-C, Cy and VP16 by 90 , 71 and 68 respectively. CONCLUSION: Chemotherapeutic drugs (Ara-C, Cy, and VP-16) induce apoptosis and meanwhile induce the activation of NF-KappaBeta in P388 cells. Glucocorticoids, such as DXM, suppress the activation of NF-KappaBeta in leukemic cells, thus increasing the apoptosis induced by chemotherapeutic drugs.
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