PI3K/Akt/NF-κB regulate ABCB1/P-glycoprotein-mediated multidrug resistance in colon carcinoma cells / 中国癌症杂志
China Oncology
;
(12): 106-111, 2014.
Article
in Chinese
| WPRIM
| ID: wpr-443907
ABSTRACT
Background and purpose:
Multidrug resistance (MDR) is the dominating obstacle to the chemotherapy. There is strong evidence that the phosphoinositide 3-kinases (PI3Ks) signaling pathway is involved in MDR phenotype, however, the mechanism of MDR occurrence is still unknown. This study tended to investigate the regulating effect of PI3K/Akt signaling pathway and its downstream target genes in P-glycoprotein (P-gp) (ABCB1 gene encoding)-mediated MDR in human colon carcinoma HCT-116/L-OHP cells.Methods:
Pretreatment with PI3K selective inhibitor LY294002 (20μmol/L) for 2 h, the sensitivity of L-OHP was evaluated by the CCK-8 (cell counting kit-8) assay in HCT-116/L-OHP cells, and the expressions of P-gp, LRP, MRP-2, Akt, p-Akt, IκB and p-IκB were evaluated by Western blot. The activity of ABCB1 promoter was evaluated by chromatin immunoprecipitation analysis (CHIP).Results:
After inhibiting the activity of PI3K/Akt signaling pathway, the IC50 value of L-OHP decreased from(157.48±16.73)μg/mL to (53.68±3.18)μg/mL in HCT-116/L-OHP cells, and the reversal index was 2.93 (P<0.01). The expressions of P-gp, p-Akt and p-IκB were down-regulation compared with the concrol group (P<0.01), but the expressions of LRP, MRP-2, Akt and IκB didn't change signiifcantly. CHIP result has conifrmed that NF-κB protein could bind to the region of ABCB1 gene promoter in HCT116/L-OHP cells.Conclusion:
Blocking of PI3K/Akt/NF-kB signal pathway could increase the drug sensitivity to MDR cells, inhibit the phosphorylation of p-Akt and p-IκB, and reversing ABCB1/P-glycoprotein-mediated multidrug resistance in colon carcinoma cells.
Full text:
Available
Index:
WPRIM (Western Pacific)
Language:
Chinese
Journal:
China Oncology
Year:
2014
Type:
Article
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