中文摘要：

建議將癌瘤轉化為良性嗜酸性細胞瘤作為潛在的抗癌策略。嗜酸性細胞瘤的一個標志是缺乏呼吸鏈復合體 I（CI）。在這里，我們通過基因剔除這一酶來誘導兩種癌癥類型的惰性，并顯示通過允許缺氧誘導因子-1α（HIF-1α）的穩定化可以逆轉這種狀態。我們進一步顯示，從長遠來看，缺乏CI的腫瘤會重新適應對缺氧的反應能力下降，這與人類嗜酸性細胞瘤的持續存在相一致。我們證明，即使缺乏CI的腫瘤無法穩定HIF-1α，它們仍然能夠存活并進行血管生成。這種適應性反應是由腫瘤相關巨噬細胞介導的，荷蘭Liposoma巨噬細胞清除清除劑clodronateliposomes清除巨噬細胞可改善CI剔除的效果。此外，通過二甲雙胍藥理學抑制CI功能和通過PLX-3397抑制巨噬細胞浸潤的同時作用，在體內協同抑制腫瘤生長，為臨床試驗中高效組合輔助療法奠定了基礎。

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：Nature Communications

時間期卷：10, Article number: 903(2019)

在線時間：2020年2月22日

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

產品信息：

貨號：CP-005-005

規格：5ml+5ml

品牌：Liposoma

產地：荷蘭

名稱：Clodronate Liposomes& Control Liposomes

辦事處：Target Technology(靶點科技)

Clodronate Liposomes氯膦酸鹽脂質體清除病腫瘤型中巨噬細胞 ，荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于Nature Communications：通過靶向線粒體復合體 I 來誘導癌癥惰性，阻斷巨噬細胞介導的適應性反應可增強其效果

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質體清除腫瘤相關巨噬細胞的材料和方法：

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).

材料和方法文獻截圖：