Sensitizing non-small cell lung cancer to BCL-xL-targeted apoptosis

Qi Shen, Jun Li, Junhua Mai, Zhe Zhang, Andrew Fisher, Xiaoyan Wu, Zhaoqi Li, Maricela R Ramirez, Shuqing Chen, Haifa Shen

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Lung cancer is the leading cause of death in the United States, with non-small cell lung cancers (NSCLC) accounting for 85% of all cases. By analyzing the expression profile of the pro-apoptotic and anti-apoptotic proteins, we have assigned NSCLCs into two distinct groups. While single agent treatment with the BCL-2/BCL-xL/BCL-w inhibitor ABT-263 (navitoclax) did not trigger apoptosis in either group, cells with a moderate to high level of MCL-1 expression were sensitive to ABT-263 treatment when MCL-1 expression was suppressed with a gene-specific siRNA. In contrast, those with a low MCL-1 expression did not undergo apoptosis upon combination treatment with ABT-263 and MCL-1 siRNA. Further studies revealed that cells with a low MCL-1 expression had low mitochondrial priming, and treatment with the chemotherapy drug docetaxel raised the mitochondrial priming level and consequently sensitized cells to ABT-263. These results establish a rationale for molecular profiling and a therapeutic strategy to treat NSCLC patients with pro-apoptotic anti-cancer drugs based on their MCL-1 expression level.

Original languageEnglish (US)
Pages (from-to)986
JournalCell death & disease
Volume9
Issue number10
DOIs
StatePublished - Sep 24 2018

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