Anlotinib exerts anti-cancer efficiency on lung cancer stem cells in vitro and in vivo through reducing NF-κB...

Area of Science:

• Oncology
• Molecular Biology
• Cancer Stem Cell Research

Background:

• Anlotinib is a known anti-cancer agent, but its effects on cancer stem cells (CSCs) remain unclear.
• Lung CSCs play a critical role in tumor growth and treatment resistance.

Purpose of the Study:

• To investigate the anti-cancer effects of anlotinib on lung CSCs in vitro and in vivo.
• To elucidate the underlying mechanisms of anlotinib's action on lung CSCs.

Main Methods:

• Isolation and identification of lung CSCs.
• In vitro and in vivo experiments including MTT assays, tumor sphere formation assays, TUNEL staining, Annexin V-FITC/PI staining, immunofluorescence, and Western blot.
• Analysis of apoptosis-related proteins (Bcl-2, Bax, cleaved caspase-3) and stemness markers (ALDH1, CD133).
• Investigation of the NF-κB signaling pathway.

Main Results:

• Anlotinib significantly inhibited the growth of lung CSCs both in vitro and in vivo.
• Anlotinib induced apoptosis in lung CSCs by down-regulating Bcl-2 and up-regulating Bax and cleaved caspase-3.
• Anlotinib decreased tumor sphere formation and expression of stemness markers (ALDH1, CD133), and sensitized CSCs to chemotherapy.
• Anlotinib suppressed the phosphorylation of NF-κB p65 and IκB-α, indicating inhibition of NF-κB activity.

Conclusions:

• Anlotinib exhibits potent anti-cancer effects against lung CSCs.
• Anlotinib acts by inducing apoptosis and attenuating stemness phenotypes.
• The mechanism involves the suppression of NF-κB signaling pathway activity.