| Peroxiredoxin ?(Prx ?)is a peroxidase reductase with atypical 2-Cys residues,belongs to the peroxiredoxin enzyme family.It has the function of removing excess reactive oxygen species(ROS)and nitric oxide(NO)from the cells and participates the physiological and pathological progressions of these cells and plays important regulatory roles to maintaining the intracellular homeostasis.The ROS and reactive nitrogen species(RNS)maintain dynamic balance under normal conditions in the cells.The accumulation of ROS and RNS in cells can cause excessive oxidative stress,which in turn affects the normal physiological state of the cells,and even induces cells to undergo apoptosis when stimulated by external conditions.In recent years,the incidence and lethality of colon cancer have increased year by year.The treatment strategy for colon cancer is still at the stage of conventional surgery,radiotherapy,and chemical drugs,and the treatment effect varies from person to person.There is a risk of incomplete removal of the lesions during surgical treatment leading to spread;radiation therapy is too heavy for the human body.Therefore,it is necessary to cooperate with the first two in order to remove hidden lesions and reduce the body load.However,chemotherapy still has some limitations,such as treatment highly costs,side effects,they also have a killing effect on normal cells,and the drug resistance-it need to increase dosing or be forced to replace different types of treatment drugs.?-lapachone is a kind of natural extract with good anticancer effect discovered in recent years,apoptosis is induced mainly by increasing the level of reactive oxygen species in cancer cells.But in the meantime,it can also inhibit topoisomerase I in cells,which can affect DNA replication and causes DNA damage to induce cell apoptosis.However,the role and molecular mechanism of Prx ? in ?-lapachone-induced colon cancer cell apoptosis are not cleariy now.Therefore,this study focused on exploring the regulatory role and molecular mechanism of Prx ? in the apoptosis of colon cancer cells induced by ?-lapachone.First,bioinformatics analysis was used to provide evidence of the correlation between Prx ? in the occurrence,development,and prognosis of human colon cancer,and,it was verified that ?-lapachone can induce apoptosis via up-regulating intracellular ROS levels in SW480 human colon cancer cells.Secondly,over-expressing Prx ? can significantly reduce ?-lapachone-induced apoptosis,which was found by evaluating Prx ? gene silencing or over-expressing cell lines.Through experiments,we found that over-expression of Prx ? can effectively inhibit the mitochondrial-dependent apoptosis pathway,which was significantly activated by ?-lapachone.In addition,analysis of the Wnt / ?-catenin signaling pathway revealed that ?-lapachone has a significant inhibitory activity to the Wnt / ?-catenin signaling pathway.The over-expression of Prx ? can effectively inhibited this inhibitory effect,thereby reducing the ?-lapachone-induced apoptosis rate of colon cancer cells significantly.In summary,?-lapachone can induce apoptosis of SW480 colon cancer cells by increasing the level of intracellular ROS and inhibiting the activity of the Wnt / ?-catenin signaling pathway.In addition,over-expression of Prx ? can significantly reduce the apoptosis of colon cancer cells caused by ?-lapachone via eliminating excessive reactive oxygen species and ulteriorly alleviating the inhibited Wnt / ?-catenin signaling pathway.This study provides new ideas for exploring the functional research of Prx ?,and lays a theoretical foundation for the application research of Prx ? in cancer treatment and the development of colon cancer treatment drugs. |
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