7月18日,，Sci Transl Med雜志報(bào)道,，強(qiáng)心甙（CGs）可通過(guò)誘導(dǎo)腫瘤細(xì)胞死亡，使之轉(zhuǎn)化為腫瘤的免疫原,，進(jìn)而促進(jìn)化療藥物的抗腫瘤效果,。
一些有效的化療藥物，特別是蒽環(huán)類(lèi)和奧沙利鉑,，誘發(fā)一種免疫原性的細(xì)胞應(yīng)激和死亡,，從而轉(zhuǎn)換病人的死亡癌細(xì)胞成為刺激抗腫瘤免疫反應(yīng)的疫苗,。
通過(guò)熒光顯微鏡研究平臺(tái)，研究者發(fā)現(xiàn)強(qiáng)心甙（CGs）是非常有效的誘導(dǎo)免疫原性細(xì)胞死亡的物質(zhì),。此效應(yīng)涉及,，對(duì)細(xì)胞膜上的Na + 和K+依賴的三磷酸腺苷酶（Na + / K +-ATPase）抑制。
CGs增強(qiáng)DNA損傷劑在免疫能力健全,，而非免疫缺陷的小鼠體內(nèi)的抗腫瘤作用,。此外，接受化療聯(lián)合CGs的癌細(xì)胞可使接種該細(xì)胞的小鼠對(duì)隨后移植的同病理類(lèi)型活腫瘤細(xì)胞具有免疫力,。
最后,，回顧性的臨床分析表明，化療期間的聯(lián)合地高辛治療對(duì)乳房癌,，大腸癌,，頭部和頸部腫瘤，以及肝癌患者生存率都可產(chǎn)生積極影響,，尤其是當(dāng)他們的治療藥物不是蒽環(huán)類(lèi)和奧沙利鉑的時(shí)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.
