Berberine restrains non-small cell lung cancer cell growth, invasion and glycolysis via inactivating the SPC25/NUF2 pathway.

Abstract

Berberine (BBR) has been proved to inhibit the malignant progression of non-small cell lung cancer (NSCLC), but the underlying molecular mechanism still needs to be further revealed. NSCLC cells (A549 and H1299) were treated with BBR. CCK8 assay, colony formation assay, flow cytometry, TUNEL staining and transwell assay were used to examine cell proliferation, apoptosis and invasion. The levels of spindle pole body component 25 (SPC25) and NDC80 kinetochore complex component (NUF2) were detected by qRT-PCR or western blot. The interaction between SPC25 and NUF2 was confirmed by Co-IP assay and FISH assay. Xenograft tumors were constructed to assess the anti-tumor role of BBR in vivo. BBR inhibited NSCLC cell growth, invasion and glycolysis. SPC25 was upregulated in NSCLC tissues, and BBR could reduce SPC25 expression in NSCLC cells. SPC25 knockdown repressed NSCLC cell growth, invasion and glycolysis, and its overexpression also reversed the anti-tumor effect of BBR. SPC25 could interact with NUF2, and NUF2 overexpression abolished the inhibitory effect of SPC25 knockdown or BBR on NSCLC cell behaviors. In animal experiments, BBR could suppress NSCLC tumor growth by inhibiting SPC25/NUF2 axis in vivo. BBR mainly played an anti-NSCLC role by targeting SPC25/NUF2 axis, which provided a new idea for NSCLC treatment.