miR-429 promotes capecitabine-resistance in pancreatic cancer PANC-1 cells by down-regulating PTEN and activating PI3K/AKT signaling pathway
10.3872/j.issn.1007-385x.2018.12.007
- VernacularTitle:miR-429通过下调PTEN并激活PI3K/AKT信号通路促进胰腺癌PANC-1 细胞对卡培他滨耐药
- Author:
HE Ping
1
;
WANG Ping
1
;
XIONG Longxin
1
Author Information
1. First Department of General Surgery, the First Hospital of Nanchang City
- Publication Type:Journal Article
- Keywords:
pancreatic cancer;
PANC-1 cell;
capecitabine;
miR-429;
PI3K/AKT signaling pathway
- From:
Chinese Journal of Cancer Biotherapy
2018;25(12):1251-1258
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To explore the mechanism of miR-429 targeting PTEN to affect capecitabine-resistance in pancreatic cancer PANC-1 cells though the PI3K/AKT signaling pathway. Methods: Capecitabine-resistant pancreatic cancer cell line PANC-1/CAP was constructed, and the expression of miR-429 and PTEN were detected by quantitative Real-time polymerase chain reaction (qRT-PCR) and Western blotting. The effect of miR-429 knock-down on cell proliferation viability, apoptosis and capecitabine-resistance was measured by colony formation assay, CCK-8 assay andAnnexin V-FITC/PI double staining flow cytometry assay, respectively. Subsequently, dual luciferase reporter assay verified that PTEN was a target gene of miR-429. Furthermore, the effect of miR-429 on PTEN-PI3K/ AKT signaling pathway was measured by Western blotting. Results: miR-429 was found to be up-regulated in PANC-1 cells and PANC-1/CAP cells compared with the non-malignant pancreatic ductal cell line (HPDE6-C7) (P<0.05 or P<0.01). Moreover, silencing of miR-429 significantly decreased cell proliferation viability, capecitabine-resistance and enhanced apoptosis of PANC-1/CAP cells; additionally, dual luciferase reporter assay confirmed that PTEN was a target of miR-429 (P<0.05 or P<0.01). Suppression of miR-429 up-regulated PTEN and blocked the PI3K/AKT signaling pathway to decrease cell proliferation viability and further reduce the capecitabine-resistance of PANC-1/CAP cells (P<0.05 or P<0.01). Conclusion: miR-429/PTEN-PI3K/AKT signaling pathway plays a certain role in regulating the capecitabine-resistance of pancreatic cancer, and inhibition of miR-429 expression may reverse the resistance of PANC-1/CAPto capecitabine.
- Full text:20181207.pdf
