Effect of LY294002 and its combination with chemotherapy drugs on the proliferation of human leukemia K562 cell line and its possible mechanism
- VernacularTitle:LY294002与化疗药物联用对白血病K562细胞多药耐药的逆转作用
- Author:
Ye ZHANG
;
Xiu-Juan QU
;
Yun-Peng LIU
;
Wei JING
;
Ke-Zuo HOU
;
Yue-E TENG
;
Jing-Dong ZHANG
;
- Publication Type:Journal Article
- Keywords:
PI3-K/Akt;
leukemia;
multidrug resistance
- From:
China Oncology
2006;0(11):-
- CountryChina
- Language:Chinese
-
Abstract:
Background and purpose:Remarkable advances have been made in cancer chemotherapy by developing new anticancer drugs and therapy strategies.However,multidrug resistance in human cancers remains a major clinical challenge for cancer treatment.Attempts in several clinical studies to reverse multidrug resistance protein (MDR) by using MDR modulators have not yet generated promising results.Our aim was to explored the mechanism of reversal of multidrug resistance in human leukemia K562 cells by PI3-K inhibitor.Methods:Trypanblue dye exclusion method was used to observe the drug sensitivity and the effect of LY294002 on the drug resistance.Western blot to analyze P-gp and p-Akt phenotypes,and flow cytometer was used to measure the intracellular drug accumulation. Results:K562/D induced by DNR was cross resistant to DNR,ADR,VCR and VP16 (Resistance Index:65,52,134 and 50 respectively).DNR induced over-expressions of P-gp and p-Akt in K562/D cells;LY294002 increased the intracellular drug accumulation,and then reversed the drug resistance to DNR,ADR,VCR and VPI6 in K562/D cells(Resistance Index:23,21,63 and 29 respectively),but not in the sensitive cells (K562/S).Conclusion:The multidrug resistance of K562/D cells can be induced by DNR which is related to the P-gp and p-Akt over-expressions, and LY294002 can reverse multidrug resistance in human leukemia cells in vitro via inhibits PI3-K/Akt pathway.
