Human recombinant RNASET2: A potential anti-cancer drug.
Human recombinant RNASET2: A potential anti-cancer drug.
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DOI：
10.18632/oncoscience.295
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Schwartz B
中科院分区：
文献类型：
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作者：
Roiz L;Smirnoff P;Lewin I;Shoseyov O;Schwartz B
细胞运动和血管生成过程在转移扩散和肿瘤侵袭性中的作用已经确定，必须同时进行靶向，以最大限度地发挥抗肿瘤药物的效力。这项工作评估了人重组RNASET2(HrRNASET2)的抗肿瘤活性，hrRNASET2是黑曲霉T2RNase ACTIBIND的同源物，已被证明具有抗肿瘤和抗血管生成活性。HrRNASET2破坏CT29结肠癌和A375SM黑色素瘤细胞内肌动蛋白细丝和富含肌动蛋白的胞外挤出组织，并诱导明显的剂量依赖性抑制A375SM细胞迁移。与阿瓦斯丁治疗的动物相比，hrRNASET2还完全阻止了血管生成素诱导的管状形成，并使HT29结直肠癌和A375SM黑色素瘤的相对体积减少了三倍。同时，hrRNASET2-VS的平均血管计数减少了36.9%。阿瓦斯丁治疗的小鼠和hrRNASET2治疗的小鼠在治疗后73天的存活率为50%，而未治疗的小鼠的中位存活时间为22天。此外，与未经治疗的动物相比，60天的hrRNASET2治疗期将A375SM肺转移灶的平均计数减少了三倍。综上所述，hrRNASET2的抗血管生成和抗肿瘤能力似乎源于它与细胞间和细胞外基质的直接相互作用，使其成为一种有吸引力的抗癌治疗候选药物。
The roles of cell motility and angiogenetic processes in metastatic spread and tumor aggressiveness are well established and must be simultaneously targeted to maximize antitumor drug potency. This work evaluated the antitumorigenic capacities of human recombinant RNASET2 (hrRNASET2), a homologue of the Aspergillus niger T2RNase ACTIBIND, which has been shown to display both antitumorigenic and antiangiogenic activities. hrRNASET2 disrupted intracellular actin filament and actin-rich extracellular extrusion organization in both CT29 colon cancer and A375SM melanoma cells and induced a significant dose-dependent inhibition of A375SM cell migration. hrRNASET2 also induced full arrest of angiogenin-induced tube formation and brought to a three-fold lower relative HT29 colorectal and A375SM melanoma tumor volume, when compared to Avastin-treated animals. In parallel, mean blood vessel counts were 36.9% lower in hrRNASET2-vs. Avastin-treated mice and survival rates of hrRNASET2-treated mice were 50% at 73 days post-treatment, while the median survival time for untreated animals was 22 days. Moreover, a 60-day hrRNASET2 treatment period reduced mean A375SM lung metastasis foci counts by three-fold when compared to untreated animals. Taken together, the combined antiangiogenic and antitumorigenic capacities of hrRNASET2, seemingly arising from its direct interaction with intercellular and extracellular matrices, render it an attractive anticancer therapy candidate.