Abstract

Endometrial cancer is increasing in prevalence worldwide. It is treated with chemotherapy and radiotherapy, in addition to surgery, but the presence of treatment-resistant tumor cells remains a barrier to effective tumor control. The purpose of this study was to develop drug-resistant cell lines using triciribine, an AKT inhibitor, and investigate the mechanism of acquired resistance. Triciribine sensitivity assays were performed using Cell Counting Kit-8 (CCK-8) on eight endometrial cancer cell lines. The chosen cell lines were highly sensitive to chemotherapy and radiotherapy. A new triciribine-resistant cell line was established and found to be highly resistant to chemotherapy. Properties of the resistant cell line were identified using molecular and cell biological techniques including CCK-8 and quantitative PCR analysis. HEC-151 had the highest triciribine sensitivity (IC50 value of 0.7±0.1 μM) of the endometrial cancer cell lines tested. We established a triciribine-resistant cell line from HEC-151 by growing cells in the presence of increasing concentrations of triciribine up to 66.6 μM. The resistant HEC-151 cells changed to spindle-shaped morphology and importantly reduced triciribine sensitivity compared to the parental cell line. ABC transporters involved in drug efflux had significantly higher expression levels in ABCB1 (1.4±0.10 times higher), ABCC1 (11.4±0.22 times higher), and ABCC4 (4.5±0.42 times higher). In this study, we established a triciribine-resistant cell line from HEC-151 cells. Our data suggest that the mechanism of drug resistance in endometrial cancer cells is attributed to the increased expression of ABC transporters.

Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call