Ligustrazine eases lung cancer by regulating PTEN and Wnt/β-catenin pathway

Lung cancer (LC) is the most common malignant tumor in the world. Ligustrazine (LSZ), an alkaloid, is an active ingredient extracted from chuanxiong Hort. Earlier studies suggested that LSZ plays a crucial role in lung diseases. The study aimed to investigate the detailed mechanism of LSZ on LC.

Protein expression was determined by qPCR, western blotting and immunohistochemistry. Cell viability was determined by CCK8 assay. Invasiveness was detected by Transwell assay. Cell growth was determined by clone formation assay. Male BALB/c nude mice were randomly divided into 2 groups (n=10): LSZ group and Control group.

Results showed that PTEN is low-expressed in lung tumor tissues and LC cells (H1650, A549, H1299, and PC-9). Appropriate doses of LSZ could significantly promote the expression of PTEN in LC cells. Besides, LSZ inhibits invasion and proliferation of H1299 cells. However, knockdown PTEN counteracts the inhibitory effect. Animal experiments suggest that LSZ inhibits tumor formation in vivo. Mechanistically, western blotting shows that LSZ treatment significantly decreased the levels of Wnt and β-catenin, while increasing the levels of PTEN and GSK-3β.

Collectively, these results demonstrate that LSZ ameliorates LC by down-regulating PTEN level and blocking Wnt/β-catenin signaling pathway.