Galectin-3C inhibits tumor growth and increases the anticancer activity of bortezomib in a murine model of human multiple myeloma.
Galectin-3C inhibits tumor growth and increases the anticancer activity of bortezomib in a murine model of human multiple myeloma.
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DOI：
10.1371/journal.pone.0021811
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Chiriva-Internati M
中科院分区：
文献类型：
--
作者：
Mirandola L;Yu Y;Chui K;Jenkins MR;Cobos E;John CM;Chiriva-Internati M
半乳糖凝集素-3是一种人类凝集素，参与许多细胞过程，包括分化、凋亡、血管生成、肿瘤转化和转移。我们评估了半乳糖凝集素- 3c，一种n端截断形式的半乳糖凝集素-3，被认为是一种主要的阴性抑制剂，作为多发性骨髓瘤（MM）的潜在治疗方法。半乳糖凝集素-3在所有9种人MM细胞系中均有不同水平的表达。在体外，半乳糖凝集素- 3c对MM细胞表现出适度的抗增殖作用，并抑制基质细胞衍生因子(SDF)-1α诱导的U266 MM细胞的趋化和侵袭。半乳糖凝集素- 3c促进硼替佐米的抗癌活性，硼替佐米是一种被FDA批准用于MM治疗的蛋白酶体抑制剂。半乳糖凝集素- 3c和硼替佐米也协同抑制mm诱导的体外血管生成活性。在U266细胞NOD/SCID小鼠MM皮下模型中，通过渗透泵静脉注射半乳糖凝集素- 3c可显著抑制肿瘤生长。在第35天，硼替佐米治疗动物的平均肿瘤体积为未治疗对照组的19.6%，半凝集素- 3c治疗动物的平均肿瘤体积为未治疗对照组的13.5%。半乳糖凝集素- 3c与硼替佐米联合使用的效果最大，在第35天，与未治疗的对照组相比，平均肿瘤体积减少了94%。综上所述，本研究首次证实半乳糖凝集素-3在人MM小鼠模型中有效。我们的研究结果表明，半乳糖凝集素- 3c单独在人MM小鼠异种移植模型中有效，并且在体外和体内增强了博特佐米的抗肿瘤活性。这些数据为继续测试半乳糖凝集素- 3c以启动治疗MM的临床试验提供了依据。
Galectin-3 is a human lectin involved in many cellular processes including differentiation, apoptosis, angiogenesis, neoplastic transformation, and metastasis. We evaluated galectin-3C, an N-terminally truncated form of galectin-3 that is thought to act as a dominant negative inhibitor, as a potential treatment for multiple myeloma (MM). Galectin-3 was expressed at varying levels by all 9 human MM cell lines tested. In vitro galectin-3C exhibited modest anti-proliferative effects on MM cells and inhibited chemotaxis and invasion of U266 MM cells induced by stromal cell-derived factor (SDF)-1α. Galectin-3C facilitated the anticancer activity of bortezomib, a proteasome inhibitor approved by the FDA for MM treatment. Galectin-3C and bortezomib also synergistically inhibited MM-induced angiogenesis activity in vitro. Delivery of galectin-3C intravenously via an osmotic pump in a subcutaneous U266 cell NOD/SCID mouse model of MM significantly inhibited tumor growth. The average tumor volume of bortezomib-treated animals was 19.6% and of galectin-3C treated animals was 13.5% of the average volume of the untreated controls at day 35. The maximal effect was obtained with the combination of galectin-3C with bortezomib that afforded a reduction of 94% in the mean tumor volume compared to the untreated controls at day 35. In conclusion, this is the first study to show that inhibition of galectin-3 is efficacious in a murine model of human MM. Our results demonstrated that galectin-3C alone was efficacious in a xenograft mouse model of human MM, and that it enhanced the anti-tumor activity of bortezomib in vitro and in vivo. These data provide the rationale for continued testing of galectin-3C towards initiation of clinical trials for treatment of MM.
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DOI：
10.1073/pnas.87.18.7324
发表时间：
1990-09-01
影响因子：
11.1
作者：
CHERAYIL, BJ;CHAITOVITZ, S;PILLAI, S
通讯作者：
PILLAI, S
影响因子：
20.3
作者：
Alsayed, Yazan;Ngo, Hai;Ghobrial, Irene M.
通讯作者：
Ghobrial, Irene M.
影响因子：
8.8
作者：
Caers, J.;Menu, E.;De Raeve, H.;Lepage, D.;Van Valckenborgh, E.;Van Camp, B.;Alvarez, E.;Vanderkerken, K.
通讯作者：
Vanderkerken, K.
DOI：
10.1084/jem.170.6.1959
发表时间：
1989-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cherayil BJ;Weiner SJ;Pillai S
通讯作者：
Pillai S
影响因子：
3.7
作者：
Chiriva-Internati M;Yu Y;Mirandola L;Jenkins MR;Chapman C;Cannon M;Cobos E;Kast WM
通讯作者：
Kast WM