Ipatasertib, an oral AKT inhibitor, inhibits cell proliferation and migration, and induces apoptosis in serous endometrial cancer.

Journal Article (Journal Article)

Ipatasertib (IPAT) is an orally administered, selective protein kinase B (AKT) inhibitor with promising data in solid tumors in both pre-clinical studies and clinical trials. Given that the PI3K/AKT/mTOR pathway is frequently dysregulated in uterine serous carcinoma (USC), we aimed to explore the functional impact of IPAT on anti-tumorigenic activity in USC cell lines and primary cultures of USC. We found that IPAT significantly inhibited cell proliferation and colony formation in a dose-dependent manner in USC cells. Induction of cell cycle arrest and apoptosis was observed in IPAT-treated ARK1 and SPEC-2 cells. Treatment with IPAT resulted in reduced adhesion and invasion of both cell lines with a concomitant decrease in the expression of Snail, Slug, and N-Cadherin. Compared with single-drug treatment, the combination of IPAT and paclitaxel synergistically reduced cell proliferation and increased the activity of cleaved caspase 3 in both cell lines. Additionally, IPAT inhibited growth in four of five primary USC cultures, and three of five primary cultures also exhibited synergistic growth inhibition when paclitaxel and IPAT were combined. These results support that IPAT appears to be a promising targeted agent in the treatment of USC.

Full Text

Duke Authors

Cited Authors

  • Buckingham, L; Hao, T; O'Donnell, J; Zhao, Z; Zhang, X; Fan, Y; Sun, W; Zhang, Y; Suo, H; Secord, AA; Zhou, C; Bae-Jump, V

Published Date

  • 2022

Published In

Volume / Issue

  • 12 / 6

Start / End Page

  • 2850 - 2862

PubMed ID

  • 35812065

Pubmed Central ID

  • PMC9251705

International Standard Serial Number (ISSN)

  • 2156-6976


  • eng

Conference Location

  • United States