Unique antitumor property of the Mg-Ca-Sr alloys with addition of Zn

Abstract

In clinical practice, tumor recurrence and metastasis after orthopedic prosthesis implantation is an intensely troublesome matter. Therefore, to develop implant materials with antitumor property is extremely necessary and meaningful. Magnesium (Mg) alloys possess superb biocompatibility, mechanical property and biodegradability in orthopedic applications. However, whether they possess antitumor property had seldom been reported. In recent years, it showed that zinc (Zn) not only promote the osteogenic activity but also exhibit good antitumor property. In our present study, Zn was selected as an alloying element for the Mg-1Ca-0.5Sr alloy to develop a multifunctional material with antitumor property. We investigated the influence of the Mg-1Ca-0.5Sr-xZn (x = 0, 2, 4, 6 wt%) alloys extracts on the proliferation rate, cell apoptosis, migration and invasion of the U2OS cell line. Our results show that Zn containing Mg alloys extracts inhibit the cell proliferation by alteration the cell cycle and inducing cell apoptosis via the activation of the mitochondria pathway. The cell migration and invasion property were also suppressed by the activation of MAPK (mitogen-activated protein kinase) pathway. Our work suggests that the Mg-1Ca-0.5Sr-6Zn alloy is expected to be a promising orthopedic implant in osteosarcoma limb-salvage surgery for avoiding tumor recurrence and metastasis.

The current trends of Mg alloys in biomedical applications—A review

“…Similarly, the Mg–0.3Ca–0.3Zn also showed a better age‐hardening response as compared to Mg–0.3Ca . The addition of Zn to Mg–Ca–Sr improved the antitumor property of the Mg–Ca‐based alloys for the biomedical application . Mg–2Ca–0.5Mn–2Zn showed better corrosion resistance as compared to Mg–2Ca and Mg–4Ca in Kokubo solution.…”

Biodegradable magnesium implants: a potential scaffold for bone tumor patients

“…Implantation of Mg scaffold is a promising solution for the treatment of OS due to the following reasons: (1) the released Mg 2+ promotes proliferation of osteoblast in vitro and accelerates the repair of premature bone in vivo [11,12]; (2) degradation products of Mg exhibit anti-tumor properties in vitro [13], and these degradation products are welltolerated in vivo; (3) the in vivo degradation cycle of Mg can be tuned from six months to several years, which matches the long-term treatment cycle of OS [14][15][16]. Previous studies demonstrated that the degradation of Mg releases Mg(OH) 2 and elevates the alkalinity of the cell culture medium [17], by which the tumor cells were killed [18,19]. However, it remains unknown if the increased alkalinity can be maintained in vivo, where the pH buffer system in the body may dampen the antitumor effect.…”

Cytotoxicity of biodegradable magnesium alloy WE43 to tumor cells in vitro: Bioresorbable implants with antitumor activity?

“…Recent reports suggest that various alloying elements can enhance the cytotoxic properties of magnesium. Wu and coauthors studied the cytotoxic effect of alloy Mg–Ca–Sr–Zn on the osteogenic sarcoma cell line U2OS. It was shown that Mg–1Ca–0.5Sr– x Zn ( x = 0, 2, 4, 6 mass %) alloys inhibit the proliferation, viability, cell cycle, migration, and invasion of U2OS cells.…”