The Dual PI3K/mToR Inhibitor Omipalisib/GSK2126458 Inhibits Clonogenic Growth in Oncogenically-transformed Cells from Neurocutaneous Melanocytosis

被引：21

作者：

Basu, Dipanjan ^{[1
]}

Salgado, Claudia M. ^{[1
]}

Bauer, Bruce ^{[2
]}

Khakoo, Yasmin ^{[3
,4
]}

Patel, Janki R. ^{[5
]}

Hoehl, Ryan M. ^{[5
]}

Bertolini, Dominique M. ^{[5
]}

Zabec, Joie ^{[5
]}

Brzozowski, Morgan R. ^{[5
]}

Reyes-Mugica, Miguel ^{[1
]}

机构：

[1] Childrens Hosp Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA

[2] North Shore Univ Hlth Syst, Div Plast & Reconstruct Surg, Northbrook, IL USA

[3] Mem Sloan Kettering Canc Ctr, Dept Pediat & Neurol, 1275 York Ave, New York, NY 10021 USA

[4] Weill Cornell Med Coll, Dept Pediat, New York, NY USA

[5] Univ Pittsburgh, Dietrich Sch Arts & Sci, Pittsburgh, PA 15224 USA

来源：

CANCER GENOMICS & PROTEOMICS | 2018年 / 15卷 / 04期

关键词：

Clonogenicity; neurocutaneous melanocytosis; MEK162; omipalisib; GENERAL THERAPEUTIC TARGET; MELANOMA; AKT; CANCER; SENSITIVITY; RESISTANCE; IGF;

D O I：

10.21873/cgp.20082

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Omipalisib has been found to affect the viability of cancer cells. However, its effect on clonogenicity - a feature of cancer stem cells, is not clear. Cells isolated from neurocutaneous melanocytosis (NCM) patients' lesions grow clonogenically. The aim of this study was to investigate the effect of omipalisib treatment on clonogenic growth of NCM cells in vitro. Materials and Methods: Clonogenic growth efficiency was evaluated by colony formation assays with or without specific growth factors. Activation of MEK and Akt was determined by immunoblots. Colony formation and cell viability were assessed upon pharmacological inhibition of MEK, Akt and mToR. Results: Clonogenicity appeared to depend on bFGF and IGF1signaling through ERK and Akt. Omipalisib treatment prevented colony formation and induced autophagic cell death. Conclusion: Signaling through Akt is important for survival of clonogenic cells in NCM, and omipalisib treatment as a monotherapy or in combination with MEK162 could be an effective therapeutic strategy to inhibit clonogenic growth.

引用

页码：239 / 248

页数：10

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