Anticancer Effect of Biodegradable Magnesium on Hepatobiliary Carcinoma: An In Vitro and In Vivo Study.

Abstract

Biliary-stent implantation has become an effective treatment for patients with malignant obstructive jaundice caused by hepatobiliary carcinoma. Stent restenosis due to tumor ingrowth is a common problem. In this study, we assessed a biodegradable form of magnesium (Mg) for its anticancer effect on hepatobiliary carcinoma, compared to the conventional stent material of titanium (Ti). The results showed that a Mg extract inhibited proliferation and induced apoptosis in human cholangiocarcinoma cells, while a Mg plate inhibited cell adhesion and destroyed the cytoskeleton in the process of biodegradation. In animal experiments with H22 tumor-bearing mice, Mg wires implanted in tumors exhibited an inhibitory effect on their growth compared with Ti wires. Fifteen days after implantation of metal wires, the mean tumor volume and weight in the Mg group were significantly smaller than in the Ti group. We observed the dynamic-degradation process of Mg wires in tumors and generation of H2 gas via soft X-ray photography and scanning electron microscopy. Histopathological analyses showed that apoptosis of tumor cells around Mg wires significantly increased, expression of carbonic anhydrase 9 significantly decreased, and the upstream protein hypoxia-inducible factor 1-alpha also decreased to some extent. Taken together, these results indicated that biodegradable Mg had antitumor properties both in vitro and in vivo, suggesting its potential application as a novel material for biodegradable biliary stents.