Faculty of Chemistry, University of Warsaw, Pasteura Str. 1, PL-02-093 Warsaw, Poland.
Faculty of Chemistry, Warsaw University of Technology, Noakowskiego Str. 3, PL-00-664 Warsaw, Poland.
Int J Mol Sci. 2021 Jan 4;22(1):439. doi: 10.3390/ijms22010439.
Nearly half of patients with advanced and metastatic melanomas harbor a mutation. Vemurafenib (VEM), a BRAF inhibitor, is used to treat such patients, however, responses to VEM are very short-lived due to intrinsic, adaptive and/or acquired resistance. In this context, we present the action of the B-Raf serine-threonine protein kinase inhibitor (vemurafenib) on the glycans structure and metallomics profiles in melanoma cells without (MeWo) and with (G-361) mutations. The studies were performed using 1-acid glycoprotein (AGP), a well-known acute-phase protein, and concanavalin A (Con A), which served as the model receptor. The detection of changes in the structure of glycans can be successfully carried out based on the frequency shifts and the charge transfer resistance after interaction of AGP with Con A in different VEM treatments using QCM-D and EIS measurements. These changes were also proved based on the cell ultrastructure examined by TEM and SEM. The LA-ICP-MS studies provided details on the metallomics profile in melanoma cells treated with and without VEM. The studies evidence that vemurafenib modifies the glycans structures and metallomics profile in melanoma cells harboring mutation that can be further implied in the resistance phenomenon. Therefore, our data opens a new avenue for further studies in the short-term addressing novel targets that hopefully can be used to improve the therapeutic regiment in advanced melanoma patients. The innovating potential of this study is fully credible and has a real impact on the global patient society suffering from advanced and metastatic melanomas.
近一半的晚期和转移性黑色素瘤患者携带 突变。维莫非尼（vemurafenib，VEM）是一种 BRAF 抑制剂，用于治疗此类患者，然而，由于内在的、适应性的和/或获得性的耐药性，VEM 的反应非常短暂。在这种情况下，我们展示了 B-Raf 丝氨酸-苏氨酸蛋白激酶抑制剂（vemurafenib）对无 突变的黑色素瘤细胞（MeWo）和有 突变的黑色素瘤细胞（G-361）的糖链结构和金属组学谱的作用。研究使用 1 酸糖蛋白（AGP），一种众所周知的急性期蛋白，和伴刀豆球蛋白 A（Con A）作为模型受体进行。通过 QCM-D 和 EIS 测量，在不同 VEM 处理下，AGP 与 Con A 相互作用后，基于频率位移和电荷转移电阻的变化，可以成功地检测到糖链结构的变化。这些变化也基于 TEM 和 SEM 检查的细胞超微结构得到证实。LA-ICP-MS 研究提供了 VEM 处理前后黑色素瘤细胞金属组学谱的详细信息。研究表明，vemurafenib 改变了携带 突变的黑色素瘤细胞的糖链结构和金属组学谱，这可能进一步暗示了耐药现象。因此，我们的数据为进一步研究短期靶向新目标开辟了新途径，希望这些目标能用于改善晚期黑色素瘤患者的治疗方案。这项研究的创新性潜力是完全可信的，对全球患有晚期和转移性黑色素瘤的患者群体产生了实际影响。
