Open AccessAnlotinib exerts anti‐cancer efficiency on lung cancer stem cells in vitro and in vivo through reducing NF‐κB activity
Author(s) -
Li Zhuohong,
Tian Juncai,
Du Lei,
Gao Ying,
Wang Yao,
You Fengming,
Wang Li
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16564
Subject(s) - cancer research , in vivo , cancer stem cell , lung cancer , annexin , apoptosis , chemistry , cisplatin , mtt assay , a549 cell , biology , microbiology and biotechnology , stem cell , pathology , medicine , biochemistry , genetics , chemotherapy
Anlotinib is a multi‐target tyrosine kinase inhibitor. Previous studies confirmed that anlotinib exerts anti‐cancer efficiency. However, the functional roles of anlotinib on cancer stem cells (CSCs) are yet to be elucidated. In this study, lung CSCs were isolated and identified in vitro, and mouse xenografts were established in vivo. MTT assays, tumour sphere formation assays, TdT‐mediated dUTP nick‐end labelling (TUNEL) staining, Annexin V‐FITC/PI staining, immunofluorescence analysis and Western blot were performed to investigate the anti‐cancer effects of anlotinib on lung CSCs. The results showed that anlotinib inhibits the growth of lung CSCs in vitro and in vivo. In addition, anlotinib induced apoptosis of these cells along with down‐regulated expression level of Bcl‐2 whereas up‐regulated Bax and cleaved caspase‐3 expression. It also sensitized lung CSCs to the cytotoxicity of cisplatin and paclitaxel; the tumour sphere formation and expression levels of multiple stemness‐associated markers, such as ALDH1 and CD133, were also decreased. Furthermore, the underlying mechanism indicated that anlotinib reduces the phosphorylated levels of NF‐κB p65 and IκB‐α in lung CSCs. Taken together, these findings suggested that anlotinib exerts potent anti‐cancer effects against lung CSCs through apoptotic induction and stemness phenotypic attenuation. The mechanism could be associated with the suppression of NF‐κB activity.