RIPK3 and cancer: Previous reports showed that RIP3 expression is frequently silenced in cancers owing to the methylation of the DNA near RIPK3 transcription start site, which was responsible for the failure of chemotherapeutics via necroptosis induction in cancer cells.35 To evaluate the potential of matrine for the treatment of CCA, which required at least low RIP3 expression, we detected the expression levels of RIP3 in CCA tissues and their paired adjacent normal liver tissues.