The Synergistic Effect Of The Hibiscus Manihot Extraction And SiO₂ Nanoparticles On The Tumor Immune Escape In Mice

The immune tolerance of tumor cells to lymphocytes is related to the expression of Fas/FasL on the cell surface.This study focused on the synergistic effect of the Hibiscus Manihot extraction and SiO₂ nanoparticles on the tumor immune escape mediated by Fas/FasL pathway,and investigated the toxic effects and related mechanisms of SiO₂nanoparticles with different sizes.Firstly,we studied the size effect of nanoparticles on the toxicity and Fas/FasL expression in immune cells and tumor cells.Next,we used RNA sequencing?RNA-Seq?analysis to investigate the effect of SiO₂ nanoparticles on the genes expression of macrophages.Finally,the combined effect of the Hibiscus Manihot extraction and SiO₂nanoparticles on the tumor immune escape related genes of tumor cells was discussed.The results are as follows:?1?SiO₂ nanoparticles had obvious size effect on cell and tissue level,and the biological effect of small size SiO2 particles was more significant.SiO2 nanoparticles could reduce the immune escape of tumor cells by reducing the FasL expression of tumor cell and increasing the expression of FasL in lymphocyte,and increase the immune killing effect on tumor cells by increasing the proportion of CD4+and CD8+type T lymphocytes.?2?In the context of whole transcriptome,we analyzed the effect of SiO₂nanoparticles on the gene expression differences in RAW264.7 cells.58,670 genes were detected by filtering and screening.There were 18 genes with significant differences,of which 5 were significantly up-regulated and 13 were significantly down-regulated,suggesting that SiO₂ nanoparticles could be used as drug carriers.From the analysis on the level of gene transcriptome,SiO₂ nanoparticles had little effect on the overall genes expression of RAW264.7 cells,only expression of some genes was changed.From the perspective of the function of differentially expressed genes,the genes related to immune activation were changed.This result suggested that SiO₂ nanoparticles could be used as an excellent drug or gene carrier for the treatment of tumors.?3?Hibiscus Manihot extraction could significantly down-regulate Fas expression and up-regulate FasL expression in B16 cells,and there was a concentration-dependent effect.Compared with the group that only added the extraction,the group added with100?g/mL 50nm SiO₂ nanoparticles significantly up-regulated the Fas expression of B16cells and down-regulated the expression of FasL,Meanwhile,spleen lymphocytes significantly enhanced the killing effect to B16 cells pretreated with SiO₂ nanoparticles and Hibiscus Manihot extraction,that existed the effect of concentration dependent.In conclusion,the synergistic effect of the Hibiscus Manihot extraction and SiO₂nanoparticles could reduce the immune escape of the tumor cells and enhance the killing effect of the immune cells on the tumor cells by interfering with the Fas/FasL apoptosis pathway.