Marin G H, Rebollo A, Bruzzoni-Giovanelli H, Schinella G, Piazzon I, Duarte A, Errecalde J
National University of La Plata - Pharmacology Department-CONICET
CIMI, Inserm/UPMC/CNRS- Université Pierre et Marie Curie, Paris 6, France; Centre d’Immunologie et des Maladies Infectieuses
J Med Life. 2017 Jul-Sep;10(3):172-175.
RAS-RAF-MEK-ERK pathway has been considered a promising target for anticancer therapy. However, tumor cells may develop resistance against such drugs via hyperactivation of N-Ras, which explains why novel therapeut-ic approaches. In this sense, the Institute Curie- Université Pierre et Marie Curie (Paris 6) designed peptides in order to disturb Ras/Raf interaction which showed pro-apoptotic properties. These peptides were patented as WO2015001045 A2 (PCT/EP2014/064243)5.
In order to check the anti-tumoral action of WO2015001045 A2 peptides in a very aggressive BALB/c mice spontaneous leukemia called LB, we performed the present study.
METHOD & RESULTS: 50 BALB/c mice inoculated with 106 LB tumor cells were randomly assigned either to control (placebo) or treatment group (that daily received 3 mg of peptide per kg of mice) during 30 days. By day 15 only 24% of the control group was alive vs. 100% of the treatment group. The average survival in treated group was 20,27 days while in control group the mean survival was 15,48 days. Either bone marrow, spleen or axillary nodes demonstrated a higher level of malignant T cell presence compare with treated group (89,78% ; 95,64% & 77,68% versus 72,45%, 80,23% & 63.44% respectively for each organ inspected.
Our study demonstrated an improvement in survival curves in mice model affected by spontaneous T lymphoid leukemia when peptides WO2015001045 A2 were used. These peptides might be a valid option to become part of the therapeutic armory for malignant lymphoproliferative diseases control.
RAS-RAF-MEK-ERK通路被认为是抗癌治疗的一个有前景的靶点。然而，肿瘤细胞可能通过N-Ras的过度激活而对这类药物产生耐药性，这就解释了为什么需要新的治疗方法。从这个意义上说，居里研究所-皮埃尔和玛丽·居里大学（巴黎第六大学）设计了肽以干扰Ras/Raf相互作用，这些肽具有促凋亡特性。这些肽已获得专利，专利号为WO2015001045 A2（PCT/EP2014/064243）5。
为了检测WO2015001045 A2肽对一种非常侵袭性的BALB/c小鼠自发性白血病（称为LB）的抗肿瘤作用，我们进行了本研究。
50只接种了106个LB肿瘤细胞的BALB/c小鼠在30天内被随机分为对照组（安慰剂）或治疗组（每天每千克小鼠接受3毫克肽）。到第15天，对照组只有24%的小鼠存活，而治疗组为100%。治疗组的平均存活时间为20.27天，而对照组的平均存活时间为15.48天。与治疗组相比，骨髓、脾脏或腋窝淋巴结中的恶性T细胞水平更高（每个检查器官分别为89.78%、95.64%和77.68%，而治疗组分别为72.45%、80.23%和63.44%）。
我们的研究表明，当使用WO2015001045 A2肽时，受自发性T淋巴细胞白血病影响的小鼠模型的生存曲线有所改善。这些肽可能是控制恶性淋巴增殖性疾病的治疗手段的一个有效选择。
