The incidence and mortality rate of lung cancer rank among the highest worldwide,severely endangering human health and life.Metformin,an anti-diabetes drug,has been shown to elicit anticancer activities in various tum...The incidence and mortality rate of lung cancer rank among the highest worldwide,severely endangering human health and life.Metformin,an anti-diabetes drug,has been shown to elicit anticancer activities in various tumors.However,its underlying mechanisms remain elusive.In this work,we explore the role of receptor-interacting protein 1(RIP1)which plays a crucial role in the process of cell death,in metformin-induced anticancer activities in lung cancer.Metformin inhibits lung cancer cell proliferation in a dose-dependent manner and promotes apoptotic cell death,as evidenced by metformin-induced PARP and caspase cleavage.Furthermore,the pan-caspase inhibitor z-VAD-fmk reverses metformin-induced cell death.Western blot and qPCR results suggest that metformin markedly downregulates RIP1 expression without affecting its mRNA and ubiquitination levels(0 vs 80 mmol/L,100%vs 20%,100%vs 15%).Additionally,co-immunoprecipitation and immunofluorescence results reveal that metformin may suppress RIP1 expression in an Hsp70-dependent manner,as metformin promotes Hsp70 degradation,and Hsp70 endogenously interacts with RIP1.Subsequent CCK-8,flow cytometry,and Western blot analyses suggest that metformin decreases Hsp70/RIP1 expression through AMPK/PKA/GSK-3βaxis.Consistently,results from a subcutaneous transplant tumor model indicate that metformin retards tumor growth without affecting mouse body weight.Collectively,these data highlight the part of RIP1 in metformin-induced anticancer activities in lung cancer in vitro and in vivo,providing novel strategy for lung cancer administration.展开更多
A rapid, ultrasensitive and convenient fluorescence measurement technology based on the enhancement of the fluorescence intensity resulting from the interaction of functionalized CdSe/CdS quantum dots （QDs） with bov...A rapid, ultrasensitive and convenient fluorescence measurement technology based on the enhancement of the fluorescence intensity resulting from the interaction of functionalized CdSe/CdS quantum dots （QDs） with bov/ne serum albumin （BSA） was proposed. The citrate-stabilized CdSe/CdS （QDs） were synthesized by using Se powder and Na2S as precursors instead of any pyrophoric organometallic precursors. The modified CdSe/CdS QDs are brighter and more stable against photobleaching in comparison with organic fluorophores. At pH 7.0, the fluorescence signal of CdSe/CdS is enhanced by increasing the concentration of BSA in the range of 0.1-10 μg/mL, and the low detection limit is 0.06 μg/mL. A linear relationship between the enhanced fluorescence peak intensity （△F） and BSA concentration （c） is established using equation △F=50.7c＋16.4 （R=0.996 36）. Results of determination for BSA in three synthetic samples are identical with the true values, and the recovery （98.9%-102.4%） and relative standard deviation （RSD, 1.8%-2.5%） are satisfactory.展开更多
文摘The incidence and mortality rate of lung cancer rank among the highest worldwide,severely endangering human health and life.Metformin,an anti-diabetes drug,has been shown to elicit anticancer activities in various tumors.However,its underlying mechanisms remain elusive.In this work,we explore the role of receptor-interacting protein 1(RIP1)which plays a crucial role in the process of cell death,in metformin-induced anticancer activities in lung cancer.Metformin inhibits lung cancer cell proliferation in a dose-dependent manner and promotes apoptotic cell death,as evidenced by metformin-induced PARP and caspase cleavage.Furthermore,the pan-caspase inhibitor z-VAD-fmk reverses metformin-induced cell death.Western blot and qPCR results suggest that metformin markedly downregulates RIP1 expression without affecting its mRNA and ubiquitination levels(0 vs 80 mmol/L,100%vs 20%,100%vs 15%).Additionally,co-immunoprecipitation and immunofluorescence results reveal that metformin may suppress RIP1 expression in an Hsp70-dependent manner,as metformin promotes Hsp70 degradation,and Hsp70 endogenously interacts with RIP1.Subsequent CCK-8,flow cytometry,and Western blot analyses suggest that metformin decreases Hsp70/RIP1 expression through AMPK/PKA/GSK-3βaxis.Consistently,results from a subcutaneous transplant tumor model indicate that metformin retards tumor growth without affecting mouse body weight.Collectively,these data highlight the part of RIP1 in metformin-induced anticancer activities in lung cancer in vitro and in vivo,providing novel strategy for lung cancer administration.
基金Project(50772133) supported by the National Natural Science Foundation of China
文摘A rapid, ultrasensitive and convenient fluorescence measurement technology based on the enhancement of the fluorescence intensity resulting from the interaction of functionalized CdSe/CdS quantum dots （QDs） with bov/ne serum albumin （BSA） was proposed. The citrate-stabilized CdSe/CdS （QDs） were synthesized by using Se powder and Na2S as precursors instead of any pyrophoric organometallic precursors. The modified CdSe/CdS QDs are brighter and more stable against photobleaching in comparison with organic fluorophores. At pH 7.0, the fluorescence signal of CdSe/CdS is enhanced by increasing the concentration of BSA in the range of 0.1-10 μg/mL, and the low detection limit is 0.06 μg/mL. A linear relationship between the enhanced fluorescence peak intensity （△F） and BSA concentration （c） is established using equation △F=50.7c＋16.4 （R=0.996 36）. Results of determination for BSA in three synthetic samples are identical with the true values, and the recovery （98.9%-102.4%） and relative standard deviation （RSD, 1.8%-2.5%） are satisfactory.
