本期Nature Communications上發(fā)表的一篇研究論文報告說,，藥物“氯沙坦”（常用來治療高血壓）能減少小鼠的腫瘤形成,。這些發(fā)現(xiàn)表明，該藥物今后對于人類癌癥的治療來說可能會被證明是有用的。
腫瘤血管為癌細(xì)胞提供營養(yǎng),，抗癌藥物的輸送最終也靠它們,。Rakesh Jain及同事發(fā)現(xiàn)，癌細(xì)胞的周圍環(huán)境會給這些腫瘤血管施加物理壓力,，這會限制血液流動和降低化療藥物向腫瘤內(nèi)滲透的能力,。他們發(fā)現(xiàn)，用“血管緊張素-II”的對抗藥“氯沙坦”（被廣泛用來治療高血壓）進(jìn)行治療,，會減少腫瘤環(huán)境中壓迫腫瘤血管的蛋白質(zhì)和復(fù)糖的生成,。這反過來又會減輕血管的收縮和幫助化療藥物“5-氟脲嘧啶”向?qū)嶒炇竽[瘤的輸送。當(dāng)用“氯沙坦”和“5-氟脲嘧啶”對患胰腺癌或乳腺癌的小鼠進(jìn)行組合治療時,，與單獨(dú)用“5-氟脲嘧啶”治療相比平均存活時間有所增加,。（生物谷Bioon.com）
生物谷推薦的英文摘要
Nature Communications DOI：10.1038/ncomms3516
Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels
Vikash P. Chauhan，John D. Martin,，Hao Liu,，Delphine A. Lacorre，Saloni R. Jain,，Sergey V. Kozin,，Triantafyllos Stylianopoulos，Ahmed S. Mousa,，Xiaoxing Han,，Pichet Adstamongkonkul，Zoran Popović,，Peigen Huang,，Moungi G. Bawendi，Yves Boucher & Rakesh K. Jain
Cancer and stromal cells actively exert physical forces (solid stress) to compress tumour blood vessels,， thus reducing vascular perfusion. Tumour interstitial matrix also contributes to solid stress,， with hyaluronan implicated as the primary matrix molecule responsible for vessel compression because of its swelling behaviour. Here we show， unexpectedly,， that hyaluronan compresses vessels only in collagen-rich tumours,， suggesting that collagen and hyaluronan together are critical targets for decompressing tumour vessels. We demonstrate that the angiotensin inhibitor losartan reduces stromal collagen and hyaluronan production， associated with decreased expression of profibrotic signals TGF-β1,， CCN2 and ET-1,， downstream of angiotensin-II-receptor-1 inhibition. Consequently， losartan reduces solid stress in tumours resulting in increased vascular perfusion. Through this physical mechanism,， losartan improves drug and oxygen delivery to tumours,， thereby potentiating chemotherapy and reducing hypoxia in breast and pancreatic cancer models. Thus， angiotensin inhibitors —inexpensive drugs with decades of safe use — could be rapidly repurposed as cancer therapeutics.
