7月18日,Sci Transl Med杂志报道,强心甙(CGs)可通过诱导肿瘤细胞死亡,使之转化为肿瘤的免疫原,进而促进化疗药物的抗肿瘤效果。
一些有效的化疗药物,特别是蒽环类和奥沙利铂,诱发一种免疫原性的细胞应激和死亡,从而转换病人的死亡癌细胞成为刺激抗肿瘤免疫反应的疫苗。
通过荧光显微镜研究平台,研究者发现强心甙(CGs)是非常有效的诱导免疫原性细胞死亡的物质。此效应涉及,对细胞膜上的Na + 和K+依赖的三磷酸腺苷酶(Na + / K +-ATPase)抑制。
CGs增强DNA损伤剂在免疫能力健全,而非免疫缺陷的小鼠体内的抗肿瘤作用。此外,接受化疗联合CGs的癌细胞可使接种该细胞的小鼠对随后移植的同病理类型活肿瘤细胞具有免疫力。
最后,回顾性的临床分析表明,化疗期间的联合地高辛治疗对乳房癌,大肠癌,头部和颈部肿瘤,以及肝癌患者生存率都可产生积极影响,尤其是当他们的治疗药物不是蒽环类和奥沙利铂的时候。(生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
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Cardiac Glycosides Exert Anticancer Effects by Inducing Immunogenic Cell Death
Laurie Menger1,2,3,Erika Vacchelli1,2,3,Sandy Adjemian1,2,3,Isabelle Martins1,2,3,Yuting Ma1,2,3,Shensi Shen1,2,3,Takahiro Yamazaki2,3,4,Abdul Qader Sukkurwala1,2,3,Micka?l Michaud1,2,3,Grégoire Mignot5,6,Frederic Schlemmer1,2,3,Eric Sulpice7,Clara Locher2,3,4,Xavier Gidrol7,Fran?ois Ghiringhelli5,6,Nazanine Modjtahedi1,2,3,Lorenzo Galluzzi2,8,Fabrice André2,9,Laurence Zitvogel2,3,4,Oliver Kepp1,2,3,*,? andGuido Kroemer
Some successful chemotherapeutics, notably anthracyclines and oxaliplatin, induce a type of cell stress and death that is immunogenic, hence converting the patient’s dying cancer cells into a vaccine that stimulates antitumor immune responses. By means of a fluorescence microscopy platform that allows for the automated detection of the biochemical hallmarks of such a peculiar cell death modality, we identified cardiac glycosides (CGs) as exceptionally efficient inducers of immunogenic cell death, an effect that was associated with the inhibition of the plasma membrane Na+- and K+-dependent adenosine triphosphatase (Na+/K+-ATPase). CGs exacerbated the antineoplastic effects of DNA-damaging agents in immunocompetent but not immunodeficient mice. Moreover, cancer cells succumbing to a combination of chemotherapy plus CGs could vaccinate syngeneic mice against a subsequent challenge with living cells of the same type. Finally, retrospective clinical analyses revealed that the administration of the CG digoxin during chemotherapy had a positive impact on overall survival in cohorts of breast, colorectal, head and neck, and hepatocellular carcinoma patients, especially when they were treated with agents other than anthracyclines and oxaliplatin.