Research Papers:
PLIN2 confers gefitinib resistance by inhibiting cell apoptosis via activation of EGFR/AKT/survivin in PC9R cells
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Abstract
Meijia Chang1,3,*, Jie Hu1,3,*, Tao Fang2,*, Jing Li1,3, Yuanlin Song1,3, Chunxue Bai1,3,4 and Jian Zhou1,3
1Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
2Department of Oncology, Shengli Oilfield Central Hospital, Dongying, China
3Shanghai Respiratory Research Institute, Shanghai, China
4State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China
*These authors contributed equally to this work
Correspondence to:
Jian Zhou, email: [email protected]
Chunxue Bai, email: [email protected]
Keywords: non-small cell lung cancer; PLIN2; gefitinib; apoptosis; TKI resistance
Received: November 01, 2017 Accepted: January 04, 2018 Published: January 10, 2018
ABSTRACT
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the first-line drugs for advanced non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. However, the development of TKI resistance is a major clinical challenge. Here we show that the adipophilin/adipose differentiation-related protein perilipin (PLIN)2 was upregulated in gefitinib-resistant PC9R cells; PLIN2 knockdown in PC9R cells conferred gefitinib resistance by inhibiting cancer cell apoptosis in vitro and in vivo and by inducing mitochondrial dysfunction and caspase activation. PLIN2 was also shown to activate EGFR/AKT/survivin signalling and was overexpressed in gefitinib-resistant cells in clinical samples. These results indicate that PLIN2 confers gefitinib resistance in lung cancer by inhibiting apoptosis and activating the EGFR/AKT/survivin pathway, and is thus a potential therapeutic target in EGFR TKI-resistant NSCLC patients.
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