Hailong Li, Hao Wang, Zong Li, Natalia Kelley, Matt Ouyang, Jia-Wei Wu, Fanguo Meng, Wen-Bin Ou
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引用次数: 0
Abstract
The incidence of gastric cancer accounts for the first malignant tumor of the digestive tract. Although some progress in gastric cancer treatments has been made, uncontrollable drug resistance makes the development of new targeted drugs and treatment options increasingly urgent. The biological function of endogenous manganese superoxide dismutase (MnSOD) has been widely studied, whereas the anti-tumor growth effects of exogenous thermostable MnSOD in gastric cancer, an oral recombinant protein drug, are still unclear. Here, compared to normal gastric epithelial cell line and enzymatic dead mutant MnSOD H29A, we show that exogenous MnSOD treatment resulted in reduction of cell viability, colony formation, migration, and invasiveness; inhibition of SGC7901 xenograft growth; induction of apoptosis and arrest of G2-phase population in gastric cancer by an enzymatic activity-dependent manner; upregulation of p53, p21, and E-cadherin; and downregulation of cyclin D1 and N-cadherin. Unexpectedly, MnSOD treatment induced zinc finger E-box homeobox 1 (ZEB1) expression in SGC7901 gastric cancer cells, which was associated with a poor five-year survival rate and poor prognosis in gastric cancer patients. However, anti-proliferative effects of exogenous MnSOD were enhanced in SGC7901 after ZEB1 knockdown, whereas attenuated in BGC823 after ZEB1 restoration. These findings indicate that the exogenous thermostable MnSOD inhibited gastric cancer growth associated with p53 and ZEB1 expression levels and highlight that the exogenous thermostable MnSOD as an oral drug warrants evaluation as a novel therapeutic strategy in gastric cancer.
期刊介绍:
Journal of Cancer is an open access, peer-reviewed journal with broad scope covering all areas of cancer research, especially novel concepts, new methods, new regimens, new therapeutic agents, and alternative approaches for early detection and intervention of cancer. The Journal is supported by an international editorial board consisting of a distinguished team of cancer researchers. Journal of Cancer aims at rapid publication of high quality results in cancer research while maintaining rigorous peer-review process.