Acquired AKT-inhibitor Resistance Is Mediated by ATP-binding Cassette Transporters in Endometrial Carcinoma

SHOJI TAKAGI & MICHIHIRO MORI et al.

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 (IC 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.
Authors
SHOJI TAKAGI, TAKAFUMI ONISHI, TSUYOSHI TAKASHIMA, KAZUKI SHIBAHARA, MICHIHIRO MORI