Inhibitory Effects And Molecular Mechanisms Of The Hypericin On RINm5F Insulinoma Cells By Bioinformatics

Insulinoma which was also known as pancreatic B cell tumor could cause an excess of insulin secretion.Therefor,the patients of insulinoma also have the symptom of hypoglycemia.Despite the cure of well locally differentiated insulinoma,the surgery cannot treat the malignant and metastatic ones.Hypericin has pharmacological activities widely,such as anti-virus,anti-depressant,anti-inflammatory and anti-tumor.Hypericin could prior accumulate in tumor cells without light and could have more significant effect on tumors when it was under light,which treats hypericin as a photosensitizer.As the moment,massive researches of photoactivated hypericin in some cancer treatment have been prompted,which inspires us to combine the photoactivated hypericin with RINm5 F insulinoma cells.Our group has make a great progress in the research on hypericin.To explore the mechanism of photoactivated hypericin on RINm5 F insulinoma cells,we utilize the measurement of RNA-seq.After the performance of correlation analysis and clustering,we find that the mode of gene expression between the photoactivated hypericin treated group and the control group has been changed.Utilizing GO function clustering with differentially expressed genes,we now show that the differentially expressed genes are clustered in categories about apoptosis,negative regulation of cell cycle,regulation of cell proliferation,TGF-beta signaling pathway,response to oxidative stress and blood vessel development.After pathway analysis about the GO categories which are listed above,we find the inhibition of photoactivated hypericin on RINm5 F insulinoma cells is chiefly through mitochondrial apoptosis,JNK signal pathway and ERK signal pathway.Furthurmore,we find that the inhibition of photoactivated hypericin on RINm5 F insulinoma cells has been decreased in their early stage whereas RINm5 F insulinoma cells recover the ability of anti-apoptosis in their late stage after a systemic time series analysis.Finally,through GO function clustering and pathway analysis of the differentially expressed genes,a mechanism model about the inhibition of photoactivated hypericin on RINm5 F insulinoma cells is built.