What question did this study set out to answer?

The aim is to investigate how ζ-Stat, a PKC-ζ inhibitor, affects glioblastoma multiforme progression.

April 5, 2026

Abstract 2924: ζ-Stat inhibits glioblastoma multiforme progression by targeting PKC-ζ/Cx43 signaling and inducing senescence.

GTGrazielly Caroline TeodoroUniversity of South Florida SRShreejana RimalUniversity of South Florida WRWishrawana S. RatnayakeUniversity of South Florida

Key Points

The aim is to investigate how ζ-Stat, a PKC-ζ inhibitor, affects glioblastoma multiforme progression.
Used cell lines T98G and U87MG to test ζ-Stat effects.
Measured proliferation rates with treatment doses of 80 μM and 40 μM.
Performed co-immunoprecipitation to confirm PKC-ζ and Cx43 association.
Conducted Western blot analysis to evaluate protein levels.
Assessed senescence via β-galactosidase activity.
ζ-Stat reduced T98G cell proliferation by 40% and U87MG by 30%.
Strong association between PKC-ζ and Cx43 was confirmed.
Inhibition of PKC-ζ/Cx43 downregulated PI3K/AKT in T98G cells.
Induced cell cycle arrest evidenced by increased p21, p27, and PTEN.
Reduced migratory potential through downregulation of vimentin.

Abstract

Abstract Glioblastoma multiforme (GBM) is a grade IV astrocytic tumor and the most aggressive form of brain cancer, marked by poor prognosis, complex vascular networks, and genomic heterogeneity. PI3K/AKT (Phosphoinositide 3-kinase/Protein Kinase B) signaling and the atypical protein kinase C isoform PKC-ζ, play essential roles in GBM cell proliferation, migration, and resistance to therapy. In addition, PKC-ζ regulates Connexin 43 (Cx43), a gap junction protein that influences cell communication, cytoskeletal organization, and tumor cell motility. This study investigated the effects of ζ-Stat (8-hydroxy-1,3,6-naphthalenetrisulfonic acid), a selective PKC-ζ inhibitor, on GBM cell lines. Treatment with ζ-Stat significantly reduced proliferation by approximately 40% in T98G cells (80 μM) and 30% in U87MG cells (40 μM) (p ≤ 0.001). Co-immunoprecipitation confirmed a strong association between PKC-ζ and Cx43 in both cell lines. Western blot analysis demonstrated that treatment with ζ-Stat reduced the levels of PKC-ζ and Cx43. As a result of PKC-ζ/Cx43 inhibition, PI3K/AKT signaling was downregulated in T98G cells. In addition, ζ-Stat induced cell cycle arrest, with increased expression of p21, p27, and PTEN, while inducing cellular senescence, as indicated by elevated β-galactosidase activity. Furthermore, ζ-Stat affected epithelial-mesenchymal transition (EMT), reducing the migratory potential of the cells through inhibition of vimentin expression. These findings highlight ζ-Stat as a promising therapeutic candidate for overcoming chemoresistance and improving treatment outcomes in glioblastoma. Citation Format: Grazielly Teodoro, Shreejana Rimal, Wishrawana S. Ratnayake, Abigail Olatunji, Mildred Acevedo-Duncan. ζ-Stat inhibits glioblastoma multiforme progression by targeting PKC-ζ/Cx43 signaling and inducing senescence abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2924.

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