中文摘要：

建議將癌瘤轉(zhuǎn)化為良性嗜酸性細(xì)胞瘤作為潛在的抗癌策略。嗜酸性細(xì)胞瘤的一個(gè)標(biāo)志是缺乏呼吸鏈復(fù)合體 I（CI）。在這里，我們通過(guò)基因剔除這一酶來(lái)誘導(dǎo)兩種癌癥類(lèi)型的惰性，并顯示通過(guò)允許缺氧誘導(dǎo)因子-1α（HIF-1α）的穩(wěn)定化可以逆轉(zhuǎn)這種狀態(tài)。我們進(jìn)一步顯示，從長(zhǎng)遠(yuǎn)來(lái)看，缺乏CI的腫瘤會(huì)重新適應(yīng)對(duì)缺氧的反應(yīng)能力下降，這與人類(lèi)嗜酸性細(xì)胞瘤的持續(xù)存在相一致。我們證明，即使缺乏CI的腫瘤無(wú)法穩(wěn)定HIF-1α，它們?nèi)匀荒軌虼婊畈⑦M(jìn)行血管生成。這種適應(yīng)性反應(yīng)是由腫瘤相關(guān)巨噬細(xì)胞介導(dǎo)的，荷蘭Liposoma巨噬細(xì)胞清除清除劑clodronateliposomes清除巨噬細(xì)胞可改善CI剔除的效果。此外，通過(guò)二甲雙胍藥理學(xué)抑制CI功能和通過(guò)PLX-3397抑制巨噬細(xì)胞浸潤(rùn)的同時(shí)作用，在體內(nèi)協(xié)同抑制腫瘤生長(zhǎng)，為臨床試驗(yàn)中高效組合輔助療法奠定了基礎(chǔ)。

英文摘要：

Converting carcinomas in benign oncocytomas has been suggested as a potential anti-cancer strategy. One of the oncocytoma hallmarks is the lack of respiratory complex I (CI). Here we use genetic ablation of this enzyme to induce indolence in two cancer types, and show this is reversed by allowing the stabilization of Hypoxia Inducible Factor-1 alpha (HIF-1α). We further show that on the long run CI-deficient tumors re-adapt to their inability to respond to hypoxia, concordantly with the persistence of human oncocytomas. We demonstrate that CI-deficient tumors survive and carry out angiogenesis, despite their inability to stabilize HIF-1α. Such adaptive response is mediated by tumor associated macrophages, whose blockage improves the effect of CI ablation. Additionally, the simultaneous pharmacological inhibition of CI function through metformin and macrophage infiltration through PLX-3397 impairs tumor growth in vivo in a synergistic manner, setting the basis for an efficient combinatorial adjuvant therapy in clinical trials.

論文信息：

論文題目：Inducing cancer indolence by targeting mitochondrial Complex I is potentiated by blocking macrophage-mediated adaptive responses

期刊名稱(chēng)：Nature Communications

時(shí)間期卷：10, Article number: 903(2019)

在線時(shí)間：2020年2月22日

DOI： doi.org/10.1038/s41467-019-08839-1

產(chǎn)品信息：

貨號(hào)：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱(chēng)：Clodronate Liposomes& Control Liposomes

辦事處：Target Technology(靶點(diǎn)科技)

Clodronate Liposomes氯膦酸鹽脂質(zhì)體清除病腫瘤型中巨噬細(xì)胞 ，荷蘭Liposoma巨噬細(xì)胞清除劑ClodronateLiposomes見(jiàn)刊于Nature Communications：通過(guò)靶向線粒體復(fù)合體 I 來(lái)誘導(dǎo)癌癥惰性，阻斷巨噬細(xì)胞介導(dǎo)的適應(yīng)性反應(yīng)可增強(qiáng)其效果

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體清除腫瘤相關(guān)巨噬細(xì)胞的材料和方法：

Depletion of macrophages

 For the clodronate treatment experiments in Fig. 7c and Supplementary Fig. 17a–d, the animals were pre-injected intraperitoneally with PBS or clodronate liposomes (100?µL, ClodronateLiposomes, Liposoma BV) on the day prior to cell injection. On the day of tumor cell injection, 5?×?106 cells in growth factor reduced matrigel (100?µL) were injected subcutaneously, immediately followed by injection of 40?µL of PBS or clodronate liposomes at the same position. The mice continued to receive intraperitoneal injection of liposomes twice weekly (100?µL).

材料和方法文獻(xiàn)截圖：