本期Nature Communications上发表的一篇研究论文报告说，药物“氯沙坦”（常用来治疗高血压）能减少小鼠的肿瘤形成。这些发现表明，该药物今后对于人类癌症的治疗来说可能会被证明是有用的。
肿瘤血管为癌细胞提供营养，抗癌药物的输送最终也靠它们。Rakesh Jain及同事发现，癌细胞的周围环境会给这些肿瘤血管施加物理压力，这会限制血液流动和降低化疗药物向肿瘤内渗透的能力。他们发现，用“血管紧张素-II”的对抗药“氯沙坦”（被广泛用来治疗高血压）进行治疗，会减少肿瘤环境中压迫肿瘤血管的蛋白质和复糖的生成。这反过来又会减轻血管的收缩和帮助化疗药物“5-氟脲嘧啶”向实验鼠肿瘤的输送。当用“氯沙坦”和“5-氟脲嘧啶”对患胰腺癌或乳腺癌的小鼠进行组合治疗时，与单独用“5-氟脲嘧啶”治疗相比平均存活时间有所增加。（生物谷）
生物谷推荐的英文摘要
Nature Communications
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 Popovi ，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.
