Gene expression profiling reveals the plausible mechanisms underlying the antitumor and antimetastasis effects of Andrographis paniculata in esophageal cancer.

ABSTRACT

Esophageal cancer (EC) is a seriously invasive malignancy with high mortality and poor prognosis. Metastasis of EC is the major cause of mortality. Our studies previously demonstrated that a herbal medicine Andrographis paniculata (AP) significantly suppressed EC growth and metastasis in vitro and in vivo. However, the underlying mechanisms responsible for these effects have not yet been systematically elucidated. In this context, gene expression profiling of AP-treated squamous EC cells (EC-109) was performed to reveal the regulatory mechanisms of AP in antitumor and antimetastasis signaling pathways using gene expression microarray analysis. Differentially expressed genes were identified by Affymetrix Gene Chip, followed by the real-time polymerase chain reaction validation. The results showed that the canonical pathways were significantly regulated by AP treatment, including multiple genes related to proliferation, apoptosis, intercellular adhesion, metastatic processes, and drug resistance, such as WNT, TGF-ß, MAPK and ErbB signaling pathways, and ATP-binding cassette transporter subfamily members. This genomic study emerges candidate molecular targets and pathways to reveal the mechanisms involved in AP's effects, which provides scientific evidence to support the clinical application of AP in EC treatment.