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腾讯登录PLoS ONE：科学家发现一种新型的摧毁癌细胞的化合物- EBC-46
| 导读 | 近日，来自QIMR伯格霍夫别墅医学研究所的研究人员通过研究，利用一种热带雨林植物的种子制成的实验性药物在前期临床试验中成功地治愈了实体瘤，相关研究刊登于国际杂志PLoS ONE上。 |
近日，来自QIMR伯格霍夫别墅医学研究所的研究人员通过研究，利用一种热带雨林植物的种子制成的实验性药物在前期临床试验中成功地治愈了实体瘤，相关研究刊登于国际杂志PLoS ONE上。
文章中，研究者Glen Boyle表示，单一剂量注射药物EBC-46会明显抑制许多人类肿瘤模型中肿瘤的生长，该药物很有可能后期将应用于病人机体的研究；将EBC-46直接注射入黑色素瘤及头颈癌等模型中可以明显抑制肿瘤。很多情况下注射单一剂量的EBC-46也会在4小时内引发癌细胞活力下降，进而最终摧毁肿瘤。
EBC-46还会部分诱发机体的细胞反应，细胞反应可以有效切断肿瘤的血液供应；在超过70%的临床前期实验中，EBC-46的效应是长期持久的，而且在长达12个月的治疗期内复发率较低。
EBC-46是从北昆士兰雨林地区的Blushwood树中提取出的一种化合物，其可以用于开发成为一种新型的实验性癌症药物，研究者Boyle表示，后期我们还需要对化合物EBC-46进行深入研究来确定其效用，目前也并没有证据显示EBC-46可以有效抑制转移性的癌症。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：
Intra-Lesional Injection of the Novel PKC Activator EBC-46 Rapidly Ablates Tumors in Mouse Models
PLoS ONE DOI: 10.1371/journal.pone.0108887Boyle GM, D'Souza MMA, Pierce CJ, Adams RA, Cantor AS, et al.
Intra-lesional chemotherapy for treatment of cutaneous malignancies has been used for many decades, allowing higher local drug concentrations and less toxicity than systemic agents. Here we describe a novel diterpene ester, EBC-46, and provide preclinical data supporting its use as an intra-lesional treatment. A single injection of EBC-46 caused rapid inflammation and influx of blood, followed by eschar formation and rapid tumor ablation in a range of syngeneic and xenograft models. EBC-46 induced oxidative burst from purified human polymorphonuclear cells, which was prevented by the Protein Kinase C inhibitor bisindolylmaleimide-1. EBC-46 activated a more specific subset of PKC isoforms (PKC-βI, -βII, -α and -γ) compared to the structurally related phorbol 12-myristate 13-acetate (PMA). Although EBC-46 showed threefold less potency for inhibiting cell growth than PMA in vitro, it was more effective for cure of tumors in vivo. No viable tumor cells were evident four hours after injection by ex vivo culture. Pharmacokinetic profiles from treated mice indicated that EBC-46 was retained preferentially within the tumor, and resulted in significantly greater local responses (erythema, oedema) following intra-lesional injection compared with injection into normal skin. The efficacy of EBC-46 was reduced by co-injection with bisindolylmaleimide-1. Loss of vascular integrity following treatment was demonstrated by an increased permeability of endothelial cell monolayers in vitro and by CD31 immunostaining of treated tumors in vivo. Our results demonstrate that a single intra-lesional injection of EBC-46 causes PKC-dependent hemorrhagic necrosis, rapid tumor cell death and ultimate cure of solid tumors in pre-clinical models of cancer.
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