Azzarito Tommaso, Lugini Luana, Spugnini Enrico Pierluigi, Canese Rossella, Gugliotta Alessio, Fidanza Stefano, Fais Stefano
Department of Drug Research and Medicine Evaluation, National Institute of Health, Rome, Italy.
SAFU Department, Regina Elena Cancer Institute, Rome, Italy.
PLoS One. 2016 Jul 22;11(7):e0159763. doi: 10.1371/journal.pone.0159763. eCollection 2016.
Tumor extracellular acidity is a hallmark of malignant cancers. Thus, in this study we evaluated the effects of the oral administration of a commercially available water alkalizer (Basenpulver®) (BP) on tumor growth in a syngenic melanoma mouse model. The alkalizer was administered daily by oral gavage starting one week after tumor implantation in CB57/BL mice. Tumors were calipered and their acidity measured by in vivo MRI guided 31P MRS. Furthermore, urine pH was monitored for potential metabolic alkalosis. BP administration significantly reduced melanoma growth in mice; the optimal dose in terms of tolerability and efficacy was 8 g/l (p< 0.05). The in vivo results were supported by in vitro experiments, wherein BP-treated human and murine melanoma cell cultures exhibited a dose-dependent inhibition of tumor cell growth. This investigation provides the first proof of concept that systemic buffering can improve tumor control by itself and that this approach may represent a new strategy in prevention and/or treatment of cancers.
肿瘤细胞外酸度是恶性肿瘤的一个标志。因此,在本研究中,我们评估了口服市售水碱化剂(Basenpulver®)(BP)对同基因黑色素瘤小鼠模型中肿瘤生长的影响。在CB57/BL小鼠肿瘤植入一周后,每天通过灌胃给予碱化剂。用卡尺测量肿瘤大小,并通过体内MRI引导的31P MRS测量其酸度。此外,监测尿液pH值以检测潜在的代谢性碱中毒。给予BP可显著降低小鼠黑色素瘤的生长;就耐受性和疗效而言,最佳剂量为8 g/l(p<0.05)。体外实验支持了体内实验结果,其中经BP处理的人源和鼠源黑色素瘤细胞培养物表现出对肿瘤细胞生长的剂量依赖性抑制。本研究首次证明了全身缓冲自身可改善肿瘤控制,且该方法可能代表了预防和/或治疗癌症的一种新策略。