LXR ligands induce apoptosis of EGFR-TKI-resistant human lung cancer cells in vitro by inhibiting Akt-NF-κB activation

LXR 配体通过抑制 Akt-NF-κB 活化诱导 EGFR-TKI 耐药人肺癌细胞体外凋亡

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作者:Siwen Liu, Haixia Cao, Dan Chen, Shaorong Yu, Huanhuan Sha, Jianzhong Wu, Rong Ma, Zhuo Wang, Changwen Jing, Junying Zhang, Jifeng Feng

Abstract

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are efficient in treating patients with non-small cell lung cancer (NSCLC) harboring EGFR activating mutations. Unfortunately, nearly all patients ultimately acquire resistance to EGFR-TKI treatment. Liver X receptors (LXRs) can regulate tumor growth in various cancer cell lines. The present study indicated that LXR agonist combined with gefitinib weakened Akt-nuclear factor (NF)-κB activation and inhibited the expression levels of apoptosis-related proteins in vitro. By contrast, LXR ligands alone exhibited no significant effect on gefitinib-resistant lung cells. In conclusion, the study provided evidence for the combination treatment of acquired TKI resistance in NSCLC.

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