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MG-:一种具有抗黑色素瘤特性和佐剂效应的新型半乳糖凝集素-3 配体。

MG-: A Novel Galectin-3 Ligand with Antimelanoma Properties and Adjuvant Effects to Dacarbazine.

机构信息

Department of Cellular Biology, Federal University of Paraná (UFPR), Curitiba 81531-980, Brazil.

Department of Chemistry, Biopol, Federal University of Paraná (UFPR), Curitiba 81531-980, Brazil.

出版信息

Int J Mol Sci. 2022 Jul 11;23(14):7635. doi: 10.3390/ijms23147635.

Abstract

Melanoma is a highly metastatic and rapidly progressing cancer, a leading cause of mortality among skin cancers. The melanoma microenvironment, formed from the activity of malignant cells on the extracellular matrix and the recruitment of immune cells, plays an active role in the development of drug resistance and tumor recurrence, which are clinical challenges in cancer treatment. These tumoral metabolic processes are affected by proteins, including Galectin-3 (Gal-3), which is extensively involved in cancer development. Previously, we characterized a partially methylated mannogalactan (MG-) with antimelanoma activities. In vivo models of melanoma were used to observe MG- effects in survival, spontaneous, and experimental metastases and in tissue oxidative stress. Analytical assays for the molecular interaction of MG- and Gal-3 were performed using a quartz crystal microbalance, atomic force microscopy, and contact angle tensiometer. MG- exhibits an additive effect when administered together with the chemotherapeutic agent dacarbazine, leading to increased survival of treated mice, metastases reduction, and the modulation of oxidative stress. MG- binds to galectin-3. Furthermore, MG- antitumor effects were substantially reduced in Gal-3/KO mice. Our results showed that the novel Gal-3 ligand, MG- has both antitumor and antimetastatic effects, alone or in combination with chemotherapy.

摘要

黑色素瘤是一种高度转移性和快速进展的癌症,是皮肤癌死亡的主要原因。黑色素瘤微环境由恶性细胞在细胞外基质上的活动和免疫细胞的募集形成,在药物耐药性和肿瘤复发的发展中发挥积极作用,这是癌症治疗中的临床挑战。这些肿瘤代谢过程受蛋白质的影响,包括半乳糖凝集素-3(Gal-3),它广泛参与癌症的发展。之前,我们对具有抗黑色素瘤活性的部分甲基化甘露聚糖(MG-)进行了表征。使用黑色素瘤的体内模型来观察 MG-在生存、自发性和实验性转移以及组织氧化应激中的作用。使用石英晶体微天平、原子力显微镜和接触角张力计进行了 MG-和 Gal-3 分子相互作用的分析测定。MG-与化疗药物达卡巴嗪联合使用时具有相加作用,导致治疗小鼠的存活率增加、转移减少和氧化应激的调节。MG-与半乳糖凝集素-3(Gal-3)结合。此外,Gal-3/KO 小鼠中的 MG-抗肿瘤作用显著降低。我们的结果表明,新型 Gal-3 配体 MG-具有抗肿瘤和抗转移作用,无论是单独使用还是与化疗联合使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8fb/9317553/f51be9ca848b/ijms-23-07635-g001.jpg

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