The mechanism of LOX promoting gastric cancer metastasis under long-term hypoxic conditions
LIANG Jin′e BAO Bowen ZHANG Xiaojie LIU Yunpeng CHE Xiaofang
Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, Department of Medical Oncologys of the First Hospital of China Medical University, Liaoning Province, Shenyang 110001, China
Abstract:Objective To investigate the mechanism of lysyl oxidase (LOX) on metastasis promotion in hypoxia-resistant gastric cancer (HRGC) cells. Methods The gastric cancer cell lines, MGC803 and BGC823 were routinely cultured. HRGC cell lines, MGC803/hypo and BGC823/hypo were cultured under 2%O2 conditions. The migration ability of gastric cancer cells was detected by Transwell assay. LOX mRNA level was detected by PCR; LOX siRNA was used for LOX transiently silencing; Western blot was used to detect the protein level of LOX, AKT and the activation of AKT pathways. Results Compared with the parental gastric cancer cells, the migration ability of HRGC cells was significantly enhanced (P < 0.05), the expression level of mRNA and protein of LOX were significantly increased (P < 0.05). After transient silencing of LOX, the migration ability was significantly decreased in HRGC cells (P < 0.05). Compared with parental gastric cancer cells, AKT phosphorylation was significantly increased (P < 0.05), whereas AKT phosphorylation was significantly decreased after transient silencing of LOX in HRGC cells (P < 0.05). Conclusion Long-term hypoxic conditions increase LOX and promote gastric cancer cell metastasis by activating the AKT pathway.
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