ABSTRACT
AIM: To investigate the ability of quercetin to reverse acquire adriamycin (ADR) resistance and explored its probably mechanism. METHODS: The CCK-8 assay was used to detect the cytotoxicity of quercetin in MCF-7/ADR cells and the reversal effect of ADR. The colony formation assay and Hoechst 332582 staining were used to detect the cell proliferation, cell apoptosis and the accumulation of rhodamine 123 (Rh123) respectively. The RNA expression levels of GAS5 and ABCB1 were detected by qRT-PCR. The protein expression levels of GSK-3β, β-catenin, c-MYC, cyclin D1, and ABCB1 were detected by Western blot. RESULTS: Quercetin (10, 20, 40 μmol/L) significantly enhanced the sensitivity of MCF-7/ADR to ADR, inhibitd cell proliferation, and increased the intracellular accumulation of Rh123. Treatment with quercetin in MCF-7/ADR cells, the expression levels of GAS5 and GSK-3β were increased, whereas the expression levels of β-catenin, c-myc, cyclin D1 and ABCB1 were decreased. Further research revealed that reduction of GAS5 by RNA interference (si-GAS5) induced inhibitory effects on the expressions of GAS5 and GSK-3β, and enhanced the expressions of β-catenin, c-myc, cyclin D1, and ABCB1. Furthermore, treatment by quercetin combined with si-GAS5 in MCF-7/ADR cells, the expressions of these proteins were effectively reversed in comparison to quercetin combined with siRNA negative control (sncRNA). CONCLUSION: Quercetin increases the expression of GAS5by GSK-3β/β-catenin signaling pathway, which inhibits the expression of ABCB1, ultimately reversing ADR resistance in the MCF-7/ADR cells.
ABSTRACT
Aim To investigate the possible mechanism of quercetin in promoting apoptosis of breast cancer cells. Methods Breast cancer cells MCF-7 were treated with quercetin. Cell viability was detected by MTT assay, cell proliferation and cloning ability were measured by plate colony formation assay, and cell apoptosis was examined by Annexin V-FITC/PI double staining assay. Meanwhile, MCF-7 cells were treated with quercetin (40, 80, 160 μmol · L
ABSTRACT
[Objective]Dysregulated long noncoding RNAs(lncRNAs)have been found involved in human diseases,including cancers. Long non-coding RNA growth arrest-specific 5(GAS5)was reported to be dysregulated in different types of cancers. Howev-er,the role of GAS5 in ovarian cancer remains elusive.[Methods]In the present study,the expression of GAS5 was detected in 108 ovarian cancer tissues and compared adjacent normal tissues by quantitative real-time PCR(qRT-PCR).[Results]The results showed that the expression levels of lncRNA GAS5 were significantly decreased in cancer tissues(P=0.0004),and it was negatively correlated with tumor size(5 cm,P<0.0001),invasion depth(T1-T2 vs. T3-T4,P=0.0021),and tumor grade(Ⅰ~Ⅱgrades vsⅢ~Ⅳgrades,P=0.0086)in ovarian cancer patients. Kaplan-Meier analysis demonstrated that decreased lncRNA GAS5 expression contributed to poor disease-free survival and overall survival.[Conclusion]In conclusion ,our study suggested that decreased lncRNA GAS5 expression may beidentified as a potential poor prognostic biomarker in ovarian cancer.