Dihydrotanshinone I Inhibits Pancreatic Cancer Progression via Hedgehog/ Gli Signal Pathway

Abstract

Introduction: Pancreatic cancer is highly fatal and its incidence is rising worldwide. Its poor prognosis is attributed to a lack of effective diagnostic and therapeutic strategies. Dihydrotanshinone I (DHT), a phenanthrene quinone liposoluble compound from Salvia miltiorrhiza Bunge (Danshen), exerts anti-tumor effects by inhibiting cell proliferation, enhancing apoptosis, and inducing cell differentiation. However, its effects on pancreatic cancer are unclear. Methods: The role of DHT in the growth of tumor cells was explored using real-time cell analysis (RTCA), colony formation assay, and CCK-8. The effects of DHT on tumor cells invasion as well as migration were assessed by Transwell and migration assays. Expressions of pro-apoptosis and metastasis factors in tumor cells were examined using western blot. Tumor apoptosis rates were studied using flow cytometry. The anticancer effect of DHT in vivo was assessed by tumor transplantation into nude mice. Results: Our analyses show that DHT has a suppressive role in epithelial-mesenchymal transition (EMT), invasiveness, proliferation, as well as migratory ability of Patu8988 and PANC-1 cells via Hedgehog/Gli signaling. Moreover, it drives apoptosis via caspases/BCL2/BAX signaling. Experiments in nude mice transplanted with tumors have shown DHT to have anticancer effects in vivo. Conclusion: Our data show that DHT effectively suppresses pancreatic cancer cell proliferation as well as metastasis, and induces apoptosis via Hedgehog/Gli signaling. These effects have been reported to be dose- and time-dependent. Therefore, DHT can be exploited as a potential treatment for pancreatic cancer.