Inhibitory effects of LOXL2 knockdown on cellular functions of liver cancer stem cells

Background: Lysyl oxidase-like 2 (LOXL2) plays a role in tumor microenvironment formation and metastasis of hepatocellular carcinoma (HCC), which has a high mortality burden. Liver cancer stem cells (LCSCs) are related with the major malignant phenotypes of HCC. The function of LOXL2 in regulation of LCSCs remains unknown. Methods: CD133(+)HepG2 and CD133(+)Hep3B cells were sorted by fluorescence-activated cell sorting (FACS) from two human hepatoblastoma cell lines. Spheroid formation, apoptosis, cell cycle, as well as transwell assays were performed upon LOXL2 knockdown in CD133(+)HepG2 and CD133(+)Hep3B cells. Protein and mRNA levels were quantified by Western blotting, immunofluorescence and reverse transcription-PCR (RT-PCR). Results: Knockdown of LOXL2 decreased spheroid formation, migration and invasion (P<0.05), also induced apoptosis ( P<0.05) and cell cycle arrest (P<0.05) in CD133(+)HepG2 and CD133(+)Hep3B cells. Knockdown of LOXL2 effectively inhibited expression of the anti-apoptosis proteins baculoviral inhibitor of apoptosis protein (IAP) repeat-containing 3 (BIRC3) and murine double minute 2 (MDM2) (P<0.01), as well as autophagy marker microtubule-associated protein 1 light chain 3 B (LC3B) and autophagy gene ATG5 in CD133(+)HepG2 and CD133(+)Hep3B cells (P<0.01). Conclusions: The results revealed that LOXL2 inhibition could reduce the proliferation and expansion of LCSCs, making LOXL2 inhibitors an attractive and novel therapeutic strategy of HCC.

Automated summary

The study found that LOXL2 inhibitors can reduce the proliferation and expansion of liver cancer stem cells and induce apoptosis and cell cycle arrest. These results provide a promising avenue for novel therapeutic strategies for HCC.