Pedro Giovana, Brasileiro Felipe César da Silva, Ferreira Rui Seabra, Bráz Aline Márcia Marques, Laufer-Amorim Renée
School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, SP, Brazil.
Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP), Botucatu, SP, Brazil.
J Venom Anim Toxins Incl Trop Dis. 2025 Apr 14;31:e20240053. doi: 10.1590/1678-9199-JVATITD-2024-0053. eCollection 2025.
Osteosarcoma is the most common primary bone tumor in humans. It is a locally aggressive tumor at the primary site, with metastasis being the main cause of death in patients. Studies on dogs have gained prominence in oncology, as they are valuable spontaneous models of osteosarcoma. In the context of natural compounds, biotoxins are attracting increasing research interest as new therapeutic agents against cancer, such as melittin, that represents 40 to 50% of the dry weight of bee venom, and studies have already shown its antitumor effects.
We analyzed the anti-migratory and anti-invasive potential of melittin, with the wound healing and Transwell tests, apoptosis with Annexin V/IP and cell viability with the MTT test in 2D and 3D models.
Melittin had a cytotoxic effect on osteosarcoma cell lines, with an IC50 between 1.5 and 2.5 µg/mL. In the wound healing test and Transwell test, melittin prevented cell migration and invasion, resulting in cell death due to iodide propidium marking in canine, murine and human cell lines. Melittin exhibited cytotoxicity in a 3D model of osteospheres, with a significantly higher IC50 in this type of culture, with values between 3.5 and 4.0 µg/mL.
We conclude that melittin has antitumor and antimetastatic properties in canine, murine and human osteosarcoma cell lines. Consequently, we believe that further research on this promising compound will facilitate its application in the development of therapeutic agents for osteosarcoma, ultimately contributing to improved survival outcomes for cancer patients.
骨肉瘤是人类最常见的原发性骨肿瘤。它在原发部位具有局部侵袭性，转移是患者死亡的主要原因。对犬类的研究在肿瘤学中日益突出，因为它们是骨肉瘤有价值的自发模型。在天然化合物的背景下，生物毒素作为抗癌新治疗剂正吸引着越来越多的研究兴趣，如蜂毒明肽，它占蜂毒干重的40%至50%，并且研究已经表明了其抗肿瘤作用。
我们通过伤口愈合试验和Transwell试验分析了蜂毒明肽的抗迁移和抗侵袭潜力，通过Annexin V/IP检测细胞凋亡，通过MTT试验在二维和三维模型中检测细胞活力。
蜂毒明肽对骨肉瘤细胞系具有细胞毒性作用，IC50在1.5至2.5μg/mL之间。在伤口愈合试验和Transwell试验中，蜂毒明肽阻止了细胞迁移和侵袭，导致犬类、鼠类和人类细胞系中碘化丙啶标记引起的细胞死亡。蜂毒明肽在骨球三维模型中表现出细胞毒性，在这种类型的培养中IC50显著更高，值在3.5至4.0μg/mL之间。
我们得出结论，蜂毒明肽在犬类、鼠类和人类骨肉瘤细胞系中具有抗肿瘤和抗转移特性。因此，我们相信对这种有前景的化合物的进一步研究将促进其在骨肉瘤治疗剂开发中的应用，最终有助于改善癌症患者的生存结果。
