当前位置： SCI文献检索 > International Journal of Clinical Oncology期刊下所有文献 > Combined antitumor effect of γ-secretase inhibitor and ABT-737 in Notch-expressing non-small cell lung cancer.

Combined antitumor effect of γ-secretase inhibitor and ABT-737 in Notch-expressing non-small cell lung cancer.

Abstract：

BACKGROUND:Inhibition of Notch by γ-secretase inhibitor (GSI) has been shown to have an antitumor effect in Notch-expressing non-small cell lung cancer (NSCLC) and to induce apoptosis through modulation of Bcl-2 family proteins. In particular, Bim, a BH3-only member of the Bcl-2 family of proteins, has an important role in the induction of apoptosis in NSCLC when cells are treated with GSI. ABT-737, a BH3-only mimetic, targets the pro-survival Bcl-2 family and also induces apoptosis. METHODS:The Notch-expressing NSCLC cell lines H460, A549, H1793, and HCC2429 were used. The combined antitumor effect of GSI and ABT-737 was evaluated using the MTT proliferation assay in vitro and in xenograft mouse models. The expression of the Notch pathway and Bcl-2 family was analyzed using Western blotting analysis when cells were treated with a single drug treatment or a combination treatment. RESULTS:GSI XX or ABT-737 alone inhibited cell proliferation in a dose-dependent manner, and combination drug treatment showed a synergistic antitumor effect in vitro. In vivo, this drug combination significantly suppressed tumor proliferation compared to the single drug treatment. Phospho-Bcl-2 was downregulated and Bax was upregulated by both the single and combination drug treatments. Bim was induced by a single drug treatment and was enhanced by combination treatment. Combination treatment-induced apoptosis was decreased by Bim inhibition, suggesting that the antitumor effect of the drug combination was dependent on Bim. CONCLUSION:Based on our data, we propose that the combination treatment is a promising strategy for NSCLC therapy.

journal_name

Int J Clin Oncol

journal_title

International journal of clinical oncology

authors

Sakakibara-Konishi J,Ikezawa Y,Oizumi S,Kikuchi J,Kikuchi E,Mizugaki H,Kinoshita I,Dosaka-Akita H,Nishimura M

doi

10.1007/s10147-016-1060-3

subject

Has Abstract

pub_date

2017-04-01 00:00:00

pages

257-268

issue

2

eissn

1341-9625

issn

1437-7772

pii

10.1007/s10147-016-1060-3

journal_volume

22

pub_type

杂志文章

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