Reversal effect of inhibiting or silencing the expression of Akt gene on hydroxycampothecin-resistance of colorectal cancer SW1116/HCPT cells / 肿瘤
Tumor
;
(12): 835-845, 2016.
Artículo
en Chino
| WPRIM
| ID: wpr-848592
ABSTRACT
Objective:
To investigate the reversal effect of blocking phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signal pathway on hydroxycampothecin (HCPT)-resistance of colorectal cancer SW1116/HCPT cells.Methods:
The expression levels of Akt and phospho-Akt (p-Akt) in the parent cell line SW1116 and HCPT-resistant cell line SW1116/HCPT were detected by Western blotting. The specific inhibitor LY294002 and siRNA targeting Akt gene were used to block the expression of Akt. Then the proliferation of SW1116/HCPT cells was detected by MTT assay. The expression levels of ATP-binding cassette transporter G2 (ABCG2) mRNA and protein were detected by real-time fluorescent quantitative PCR and Western blotting, respectively. The drug-efflux function was detected by Rhodamine 123 (Rh123) method.Results:
The expression level of p-Akt in SW1116/HCPT cells was higher than that in parent SW1116 cells (P < 0.01). LY294002 and Akt-siRNA could inhibit the expression level of p-Akt, suppress the proliferation of SW1116/HCPT cells, and increase the sensitivity to HCPT (all P < 0.01). LY294002 could down-regulate the expressions of ABCG2 mRNA and protein by (74.82±4.71)% and (58.24±4.78)% (both P < 0.01), respectively. The accumulation of Rh123 in SW1116/HCPT cells was increased 1.45±0.12 times 48 h after treatment (P < 0.01). After silencing the expression of Akt, the expressions of ABCG2 mRNA and protein were decreased by (59.63±5.14)% and (44.41±2.56)% (both P < 0.01), respectively, and the concentration of intracellular Rh123 was increased 1.22±0.10 times (P < 0.01).Conclusion:
PI3K/Akt signal pathway can up-regulate the expression of drug-resistance gene ABCG 2, and play a vital role in the carcinogenesis of multidrug-resistance induced by HCPT.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Idioma:
Chino
Revista:
Tumor
Año:
2016
Tipo del documento:
Artículo
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