基于免疫原性细胞死亡探讨中药抗肿瘤新机制

Study on New Mechanism of Antitumor Chinese Medicine Based on Immunogenic Cell Death

免疫原性细胞死亡(immunogenic cell death,ICD)是一种免疫激活的特殊细胞死亡形式。中药ICD诱导剂如紫草素、姜黄素、白藜芦醇、异槲皮苷、欧夹竹桃苷、雷公藤红素等单体及其载药纳米颗粒、联合疗法通过促使濒死的肿瘤细胞释放损伤相关分子模式(danger associated molecular patterns,DAMPs),招募并活化免疫细胞,使抗肿瘤治疗取得长远的疗效。其上游机制包括诱导肿瘤细胞发生基于活性氧的内质网应激,调控NF-κB、PI3K/Akt/mTOR、AMPK、JAK/STAT等通路,诱导细胞凋亡、焦亡、铁死亡、坏死性凋亡或调控自噬。中药诱导ICD作为一种更加安全、高效的肿瘤治疗方式,通过“祛邪以扶正”的新颖机制,为中医药抗肿瘤治疗开拓了新的思路。

Immunogenic cell death(ICD)is a special type of cell death under the condition of immune system being activated.ICD Chinese medicine inducers such as shikonin,curcumin,resveratrol,isoquercitrin,oleandrin,celastrol and other monomers,their drug-carrying nanoparticles,and their combined therapies can promote the release of damage associated molecular patterns(DAMPs)in dying tumor cells,recruit and activate immune cells,so as to achieve long-term efficacy in anti-tumor therapy.Its upstream mechanisms include inducing endoplasmic reticulum stress based on reactive oxygen species in tumor cells,regulating NF-κB,PI3K/Akt/mTOR,AMPK,JAK/STAT pathways,inducing apoptosis,pyroptosis,ferroptosis,necrotic apoptosis or regulating autophagy.As a safer and more efficient way to treat cancer,Chinese medicine inducing ICD opens up a new idea for anti-tumor Chinese medicine therapy through the mechanism of removing pathogens to support healthy qi in the field of traditional Chinese medicine.