Abstract

BACKGROUND: Baicalin, one of the main bioactive components extracted from the traditional Chinese medicine baical Skullcap root, has an anti-tumor activity which had been studied in several cancers. However, its role in human mesothelioma remains unknown. In this study, we investigated the anti-tumor mechanisms of baicalin in the mesothelioma cell line MESO924.

MATERIAL AND METHODS: Effects of baicalin on mesothelioma were assessed by measuring cell viability, apoptosis, migration, invasion, inactivation of signaling intermediates, and cell-cycle alterations.

RESULTS: Baicalin inhibited the proliferation, migration, and invasion of human mesothelioma cells and increased their apoptosis, all in a dose-dependent manner. Specifically, baicalin decreased the expression of p-EGFR, p-AKT, p-MAPK, p-S6, Bcl-2, and VEGF and increased the expression of Bax in mesothelioma cells. The suppressed mesothelioma cellular proliferation is due to the arrest of the S cell cycle by baicalin. Inhibition of the PI3K/AKT/mTOR signaling pathway by a PI3K/AKT/mTOR inhibitor augmented the anti-proliferation effects induced by baicalin. In addition, baicalin increased the sensitivity of MESO924 to the chemotherapeutic drugs doxorubicin, cisplatin, and pemetrexed.

CONCLUSIONS: These results highlight the roles of baicalin in inhibiting cell growth, migration, and invasion of mesothelioma cells while increasing apoptosis and sensitizing cells to chemotherapeutic agents through the PI3K/AKT/mTOR signaling pathway, which indicates that baicalin could be a useful drug for mesothelioma therapy.

Keywords: Chinese traditional medicine, Mesothelioma, Baicalin, PI3K/AKT/mTOR Signaling Pathway, Cell Cycle, Neoplasm Invasiveness, Proto-Oncogene Proteins c-akt, Proto-Oncogene Proteins c-bcl-2, TOR Serine-Threonine Kinases