Canitano Andrea, Iessi Elisabetta, Spugnini Enrico Pierluigi, Federici Cristina, Fais Stefano
Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
SAFU, Regina Elena Cancer Institute, Rome, Italy.
Cancer Lett. 2016 Jul 1;376(2):278-83. doi: 10.1016/j.canlet.2016.04.015. Epub 2016 Apr 12.
Multiple Myeloma (MM) is the second most common hematological malignancy and is responsive to a limited number of drugs. Unfortunately, to date, despite the introduction of novel drugs, no relevant increase in survival rates has been obtained. Proton pump inhibitors (PPIs) have been shown to have significant antitumor action as single agents as well as in combination with chemotherapy. This study investigates the potential anti-tumor effectiveness of two PPIs, Lansoprazole and Omeprazole, against human MM cells. We found that Lansoprazole exerts straightforward efficacy against myeloma cells, even at suboptimal concentrations (50 µM), while Omeprazole has limited cytotoxic action. The Lansoprazole anti-MM effect was mostly mediated by a caspase-independent apoptotic-like cytotoxicity, with only a secondary anti-proliferative action. This study provides clear evidence supporting the use of Lansoprazole in the strive against MM with an efficacy proven much higher than current therapeutical approaches and without reported side effects. It is however conceivable that, consistent with the results obtained in other human tumors, Lansoprazole may well be combined with existing anti-myeloma therapies with the aim to improve the low level of efficacy of the current strategies.
多发性骨髓瘤（MM）是第二常见的血液系统恶性肿瘤，仅对少数几种药物有反应。不幸的是，迄今为止，尽管引入了新药，但生存率并未得到显著提高。质子泵抑制剂（PPI）已被证明作为单一药物以及与化疗联合使用时具有显著的抗肿瘤作用。本研究调查了两种PPI（兰索拉唑和奥美拉唑）对人MM细胞的潜在抗肿瘤效果。我们发现，即使在次优浓度（50µM）下，兰索拉唑对骨髓瘤细胞也具有直接的疗效，而奥美拉唑的细胞毒性作用有限。兰索拉唑的抗MM作用主要由不依赖半胱天冬酶的凋亡样细胞毒性介导，仅具有次要的抗增殖作用。本研究提供了明确的证据，支持在对抗MM的斗争中使用兰索拉唑，其疗效已被证明远高于目前的治疗方法，且未报告有副作用。然而，可以想象，与在其他人类肿瘤中获得的结果一致，兰索拉唑很可能与现有的抗骨髓瘤疗法联合使用，以提高当前策略的低疗效水平。
