摘要Colorectal cancer(CRC),one of the leading causes of cancer-related mortality globally,ur-gently requires complementary and alternative therapies.Ferroptosis,an iron-dependent form of regulated cell death driven by lipid peroxidation,has emerged as a promising anti-cancer strategy.Dendrobium officinale(D.officinale),a renowned traditional Chinese medicin-al herb,is widely used in several Asian countries for its nutritional and therapeutic benefits.Although D.officinale has demonstrated anti-tumor effects,the molecular mechanisms under-lying its action against CRC remain incompletely characterized.This study aimed to elucidate the role of D.officinale in suppressing CRC through the induction of ferroptosis and its regu-latory effects on glutathione peroxidase 4(GPX4),a key suppressor of ferroptosis.In vitro as-says were conducted using HCT116 and SW480 CRC cell lines,and in vivo efficacy was evalu-ated in BALB/c nude mice bearing CRC xenografts.D.officinale significantly reduced CRC cell viability and proliferation in vitro and suppressed tumor growth in vivo.Induction of ferrop-tosis was evidenced by elevated levels of Fe2+,malondialdehyde(MDA),and lipid peroxida-tion,along with a depleted glutathione/oxidized glutathione disulfide(GSH/GSSG)ratio.Not-ably,these effects were reversed by ferroptosis inhibitors,including ferrostatin-1(Fer-1)and deferoxamine.Consistently,D.officinale markedly downregulated GPX4 expression.Overex-pression of GPX4 rescued D.officinale-induced ferroptosis,whereas GPX4 silencing exacer-bated this effect.D.officinale suppresses CRC by triggering GPX4-dependent ferroptosis,providing a novel,naturally derived therapeutic approach.These findings bridge traditional medicine and modern oncology,establishing a foundation for developing targeted CRC treat-ments.