Dihydroartemisinin regulates the apoptosis and growth of colorectal cancer by suppressing DPYSL2 and increasing TF and ACHE

Abstract

Colorectal cancer (CRC) is considered a tumor of the digestive tract with high incidence and great danger. The complex pathogenesis of CRC has led to a lack of effective therapies and drugs in clinical practice. Study found that dihydroartemisinin (DHA) may selectively kill tumor cells by increasing the expression of transferrin receptors on tumor cell membranes. The intersection targets of DHA and CRC were analyzed by bioinformatics. Cell experiments were used to validate the results of bioinformatics. Flow cytometry was uesd to examine effect of DHA on apoptosis of SW480 cancer cell, the total RNA from cancer cell was used for transcriptome sequencing analysis. The binding stability of DHA to protein targets was verified through molecular docking. Binding free energy, hydrogen bonds and root-mean-square fluctuations were analyzed by molecular dynamics. Core interaction protein targets were screened and analyzed by PPI, GO and KEGG. Cell experiments showed that DHA promoted apoptosis in SW480 cancer cell, results of transcriptome sequencing showed that DHA significantly up-regulated gene expression of TF and ACHE, while a down-regulated gene expression of DPYSL2. Molecular docking showed that DHA bound tightly to TF, ACHE and DPYSL2. Binding stability of dihydroartemisinin to protein targets was demonstrated by molecular dynamics. This study found that DHA may not only affect the apoptosis of CRC by regulating TF, but also hinder the growth and migration of CRC through ACHE and DPYSL2. The mechanism of DHA treating CRC was investigated by bioinformatics analysis, cellular experiments, transcriptome sequencing and supercomputer simulation.