Doxorubicin-induced Senescence of Colon Cancer Cell Promotes NK Cell Activation
To improve the anti-tumor mechanism of doxorubicin,this study investigated the influence and reasons of doxorubicin-induced colon cancer cell senescence on NK cell activity in the tumor microenvironment.Firstly,the effect of doxorubicin on both cel-lular and animals enescence was verified.Secondly,it was found that doxorubicin-induced colon cancer cell senescence can enhance the activation of NK cells in the subsequent co-incubation system of splenic lymphocytes/tumor infiltrating lymphocytes(TIL).To investigate the reason for NK cell activation,transcriptomic detection and analysis on doxorubicin induced senescent colon cancer cells was couducted,and the analysis results were further validated.It was found that the mRNA level of IL-7 in senescent colon cancer cells was significantly increased.Subsequent exploration revealed that IL-7 can significantly promote the increase of NK cell activation index CD69.In summary,a certain concentrations of doxorubicin can induce colon cancer cell senescence,which promote the activation of NK cells by secreting IL-7,which may be an important reason for doxorubicin's inhibition of colon cancer cells.Results of this study have expanded the immunomodulatory anti-tumor mechanism of doxorubicin,providing experimental evidence for its rational clinical application.
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