根據(jù)一項于2012年7月18日發(fā)表在Science Translational Medicine期刊上的研究，一類被稱作強心苷(cardiac glycosides)的心臟病藥物能夠誘導(dǎo)免疫原性細胞死亡(immunogenic cell death, ICD),，并以此將死亡的癌細胞轉(zhuǎn)化為一種刺激抗腫瘤反應(yīng)的疫苗,。
來自法國國家健康與醫(yī)學(xué)研究院的Laurie Menger和同事們開發(fā)出并利用一種基于自動化表面熒光顯微技術(shù)(epifluorescence microscopy)的平臺來鑒定免疫原性細胞死亡(ICD)的誘導(dǎo)劑。
研究人員發(fā)現(xiàn)強心苷是一類強效的ICD誘導(dǎo)劑,，而且這種效果與抑制細胞膜中的鈉鉀依賴性三磷酸腺苷酶相關(guān)聯(lián),。在具有免疫能力的小鼠體內(nèi)，它們的抗癌效果只有與DNA損傷性試劑一起使用時才能夠看得到,。經(jīng)過化療藥物和強心苷處理過的癌細胞能有效地作為經(jīng)過活的同類型癌細胞激發(fā)的小鼠的疫苗,。此外，對145名接受強心苷治療的癌癥患者和290名沒有接受強心苷治療的癌癥患者進行的一項回顧性分析表明接受強心苷治療的患者5年存活率得到改善(風(fēng)險比為0.62),。
Menger和同事們寫道,，“確定一大類細胞毒性試劑擁有誘導(dǎo)ICD的能力將是令人感興趣的，因此這有助于人們鑒定出引發(fā)一種免疫學(xué)上旁觀者效應(yīng)(bystander effect)的新藥物,。再者,，在藥物開發(fā)生產(chǎn)線中，基于它們促進ICD的能力,，人們也可能明智地決定在臨床上開發(fā)出擁有相同靶標(biāo)和作物機制的化合物,。”(生物谷：Bioon.com)
本文編譯自Heart medication converts cancer cells into vaccine
doi: 10.1126/scitranslmed.3003807
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PMID:
Cardiac Glycosides Exert Anticancer Effects by Inducing Immunogenic Cell Death
Laurie Menger1,2,3, Erika Vacchelli1,2,3, Sandy Adjemian et al.
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.
