Combined treatment with EGFR inhibitors and arsenite upregulated apoptosis in human EGFR-positive melanomas: role of suppression of the PI3K-AKT pathway (Oncogene, 24:616-626, 2005)

報告日期: 2005/10/28
報告時間: 16:00/16:50
報告學生: 曾鴻裕
講評老師: 凌 斌
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Combined treatment with EGFR inhibitors and arsenite upregulated apoptosis in human EGFR-positive melanomas: a role of suppression of the PI3K-AKT pathway

Oncogene (2005) 24, 616–626

Speaker: 曾鴻裕                               Time: 2005/10/28 PM: 4:00

Commentator: 凌斌  老師                      Place: Room 602

 

Abstract

    Epidermal growth factor receptor (EGFR) was an important target in anticancer drug due to its ability to control tumor cell proliferation and to suppress apoptosis. As it was previously observed for several types of cancer, like non-small-cell lung cancer, specific inhibitors of EGFR-mediated signaling may reduce antiapoptotic properties of cancer cells and sensitize them to cytotoxic drugs. In recently reported that arsenite combination with inhibitors of the PI3K-AKT and mitogen-activated protein kinase (MAPK) kinase (MEK)-extracellular signal-regulated kinase (ERK) pathways, could induce high levels of apoptosis in different melanomas. EGFR signaling operates via activation of the PI3K-AKT and MEK-ERK pathways. Combination of arsenite and EGFR inhibitors might also effectively induce apoptosis in melanoma. The authors demonstrate that a moderate concentration of arsenite (5–10 mM) indeed upregulates apoptosis induced by EGFR inhibitors in EGFR-positive melanomas. In contrast, induction of apoptosis in melanomas with few EGFR surface expressions or with defective EGFR signaling requires direct suppression of the PI3K-AKT and MAPK pathways by specific pharmacological inhibitors in the presence of arsenite. Under these conditions, metastatic melanoma cell lines undergo TNF-related apoptosis inducing ligand (TRAIL) and tumor necrosis factor alpha (TNFa)-mediated apoptosis. Taken together, these data provide additional approaches in sensitizing melanomas to the cytotoxic effects of specific inhibitors of survival pathways.

 

References

Vladimir N. Ivanov and Tom K. Hei. Arsenite Sensitizes Human Melanomas to Apoptosis via Tumor Necrosis Factor a-mediated Pathway. J Biol Chem. 2004; 279: 22747-58.

 

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