PI3K pathway inhibitor LY294002 alters Jurkat T cell biobehaviours via ERK1/2-ICBP90 mediation

Abstract

Abstract:Little is known about whether there is a relationshipbetweenPI3K/AKT, ERK1/2 and an inverted CCAAT box binding protein (ICBP90) in biological behaviours of tumour cells. The aim of this study was to determine thisusing Jurkat T cells. Compared to PD98059 (an ERK1/2 signaling inhibitor), DAPT (a Notch signaling inhibitor) or adriamycin (a classical anti-tumour drug), the inhibition of Jurkat T cell growth by LY294002 (a PI3K/Akt signaling inhibitor) was more obvious. LY294002 combined with adriamycin appeared to have a synergistic effect. LY294002 strongly blocked Jurkat T cells at each phase of cell cycle with a decrease of DNA content, superior to adriamycin. Consistent with these changes, the expression of phosphorylated ERK1/2 was markedly decreased in the LY294002-treated Jurkat T cells, leading to the reduction of ICBP90 production, followed by moderate attenuation of TGF-β secretion. The results suggest that deactivation of PI3K/Akt signalling can surpress Jurkat T cell growth through inhibiting cell proliferation and blocking the cell cycle. ICBP90 may mediate the PI3K/AKT-ERK1/2 signalling to regulate leukemia cell growth.

Cathepsin L-induced galectin-1 may act as a proangiogenic factor in the metastasis of high-grade serous carcinoma

“…Gal1-induced HOMEC proliferation was significantly reduced by the two MEK1/2 inhibitors and the PI3K inhibitor LY294002, but not the selective AKT inhibitor MK2206. It is possible that the latter result was observed due to cross-reactivity of LY294002 with the ERK1/2 pathway and thus inhibition of ERK1/2 phosphorylation [35]. Taken together, our data suggest that ERK1/2 pathway is involved in the HOMEC proliferation induced by exogenous Gal1 (Fig.…”

Cathepsin L Induces Proangiogenic Changes in Human Omental Microvascular Endothelial Cells via Activation of the ERK1/2 Pathway

“…In the subsequent experiments, we showed that the two MEK1/2 inhibitors significantly reduced or abolished CathL-induced HOMEC proliferation over 72 h. This observation was replicated in in the presence of LY294002 (PI3K inhibitor) but not with the selective AKT inhibitor MK2206. This is perhaps not surprising as LY294002 is known to cross-react with the ERK1/2 pathway where it inhibits ERK1/2 phosphorylation [41]. Thus, it is possible that LY294002 in fact inhibited activation of ERK1/2 and reduced HOMEC proliferation, and that AKT is not involved in the induction of cell proliferation as the AKT-specific inhibitor failed to reduce this proangiogenic response.…”