Sensitizing cGAS-STING pathway by manganese dioxide with low levels of doxorubicin
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초록
내용
Recent cancer immunotherapeutic researches have focused on cyclic GMP-AMP (cGAMP) synthase (cGAS) and stimulator of interferon genes (STING) pathway for activation of antitumor immunity using innate immune. The cGAS-STING pathway can stimulate secretion of pro-inflmmatory cytokines and activation of antigen-presenting cells and immune cells such as natural killer cells and T cells. Manganese ion (Mn2+), which increases the sensitivity of cGAS to double-stranded DNA, its enzymatic acvity and binding affinity between cGAMP and STING, can be used to maximize the role of cytosolic DNA sensor. In this research, doxorubicin (DOX) was used for inducing cytosolic DNA to damage nuclear DNA and the cytosolic DNA was binded with cGAS to activate the following pathway. Mn2+ could sensitize the cGAS-STING pathway with low levels of DOX, although low levels of DOX could not induce enough cytosolic DNA to activate the antitumor activity.