Tong Zhang: Department of Occupational Health, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province 150086, PR China.
Yue Wang: Department of Occupational Health, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province 150086, PR China.
Yangyang Chen: Department of Occupational Health, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province 150086, PR China.
Ying Gao: Department of Occupational Health, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province 150086, PR China.
Dan Zhang: Department of Occupational Health, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province 150086, PR China.
Shuo Jin: Department of Occupational Health, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province 150086, PR China.
Wenxue Yao: Department of Occupational Health, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province 150086, PR China.
Lina Li: Department of Occupational Health, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province 150086, PR China.
Shikuan Yang: Department of Occupational Health, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province 150086, PR China.
Yonghui Wu: Department of Occupational Health, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province 150086, PR China. Electronic address: wuyonghui777@163.com.
Nickel (Ni) compounds is recognized industrial carcinogen, which could increase the risk of lung cancer in Ni refineries workers. However, the underlying carcinogenic mechanism still remains to elucidate. Metformin has shown the anticancer properties through suppressing aerobic glycolysis. In the present study, we evaluated the effect of Ni-refining fumes exposure on aerobic glycolysis and the role of AMPK/GOLPH3, as well as how metformin alleviated nickel-induced aerobic glycolysis in vitro and vivo. Firstly, Beas-2B cells were exposed to different concentrations of Ni-refining fumes and pretreated with metformin (activation of AMPK), compound C (AMPK inhibitor) in vitro. Our findings indicated that Ni fumes expose evoked aerobic glycolysis by AMPK/GOLPH3, while metformin attenuated Ni particles-promoted GOLPH3-mediated aerobic glycolysis by p-AMPK expression increase. Then Mito-TEMPT (a mitochondria-targeted antioxidant) and lipopolysaccharide (LPS, ROS activator) were pretreated to affect ROS production in Beas-2B cells. Ni-induced ROS prevented AMPK activation. Moreover, C57BL/6 mice were exposed to 2 mg/kg Ni by non-exposed endotracheal instillation and metformin (100, 200 and 300 mg/kg) via oral gavage for 4 weeks. The effects of AMPK/GOLPH3 axis on Ni-induced aerobic glycolysis were assessed. The results indicated that metformin decreased the protein levels of GOLPH3, LDHA, HK2, MCT-4 and improved p-AMPK expression. Thus, our findings demonstrated metformin antagonized Ni-refining fumes-caused aerobic glycolysis via AMPK/GOLPH3.
