BackgroundGastric cancer, as a multifactorial disorders, shows cytological and architectural heterogeneity compared to other gastrointestinal cancers, making it therapeutically challenging. Cisplatin is generally used in clinic for gastric cancer treatment but with toxic side effects and develops resistance. Anti-tumor properties of copper and its coordinated compounds have been explored intensively in recent years.MethodsIn this study, we synthesized a novel Schiff base copper coordinated compound (SBCCC) and examined its antitumor effects in two gastric cancer cell lines SGC-7901 and BGC-823 as well as a mouse model of gastric cancer.ResultsThe results show that SBCCC can significantly inhibit the proliferation of gastric cancer cells in a dose- and time-dependent manner. The IC50 of SBCCC in SGC-7901 and BGC-823 cells is 1M, which is much less than cisplatin's IC50. SBCCC induces apoptosis and causes cell cycle arrest at the G1 phase. SBCCC induces apoptosis via multiple pathways including inhibition of NF-B, ROS production and autophagy.ConclusionsThe synthesized SBCCC induced cancer cell death via inhibition of NF-B, ROS production and autophagy. The multiple cell-killing mechanisms were important to overcome therapeutic failure because of multidrug-resistance of cancer cells. SBCCC, with a lower IC50 compared to cisplatin, could render it the potential to overcome the side-effect for clinical application.
[1]Jilin Univ, Hosp 1, Dept Gastroenterol, 71 Xinmin St, Changchun 130021, Jilin, Peoples R China.
[2]Jilin Univ, Hosp 1, Dept Hepatobiliary & Pancreas Surg, Changchun, Jilin, Peoples R China.
[3]Jilin Univ, Coll Basic Med Sci, Changchun 130021, Jilin, Peoples R China.
[4]Univ Louisville, Dept Surg, Div Surg Oncol, Louisville, KY 40202 USA.
(8.0+极速模式)