Hiramoto Keiichi, Oikawa Hirotaka
Department of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagaki, Suzuka 513-8607, Japan.
Int J Mol Sci. 2024 Nov 28;25(23):12800. doi: 10.3390/ijms252312800.
Melanomas, which develop on malignant transformations of melanocytes, are highly malignant and prone to metastasis; therefore, effective drugs are required. The (MC) extract has been shown to suppress cancer cell proliferation and invasion; however, the effect of the MC extract on melanoma in living organisms remains unclear. In this study, we investigated the mechanism underlying the amelioration of melanoma cell extravasation into mouse lungs by the MC extract. Male C57BL/6j mice (aged 8 weeks) were injected with B16 melanoma cells (1 × 10 cells/mouse). Subsequently, they were orally administered the MC extract daily for 2 weeks; mouse lung samples were obtained on the final day and analyzed. The MC extract ameliorated melanoma proliferation and infiltration into the lungs caused by melanoma cell treatment. It also increased phosphatase and tensin homolog deletion from chromosome 10 and suppressed paired box gene 3 (PAX3) and the phosphatidylinositol trisphosphate/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin complex 1 signaling. Furthermore, it decreased microphthalmia-associated transcription factors and induced the suppression of cyclin-dependent kinase 2, hepatocyte growth factor receptor, B-cell/CLL lymphoma 2, and Ras-related proteins. Our findings suggest that the MC extract suppresses tumor survival genes by regulating PAX3, thereby ameliorating melanoma proliferation and invasion.
黑色素瘤由黑素细胞恶性转化形成,具有高度恶性且易于转移,因此需要有效的药物。已证明(MC)提取物可抑制癌细胞增殖和侵袭;然而,MC提取物对活生物体中黑色素瘤的作用仍不清楚。在本研究中,我们研究了MC提取物改善黑色素瘤细胞渗入小鼠肺部的潜在机制。将8周龄的雄性C57BL/6j小鼠注射B16黑色素瘤细胞(1×10个细胞/只小鼠)。随后,每天对它们口服给予MC提取物,持续2周;在最后一天获取小鼠肺样本并进行分析。MC提取物改善了黑色素瘤细胞处理引起的黑色素瘤增殖和肺部浸润。它还增加了第10号染色体上的磷酸酶和张力蛋白同源物缺失,并抑制了配对盒基因3(PAX3)以及磷脂酰肌醇三磷酸/RAC-α丝氨酸/苏氨酸蛋白激酶/雷帕霉素复合物1信号通路。此外,它减少了小眼相关转录因子,并诱导细胞周期蛋白依赖性激酶2、肝细胞生长因子受体、B细胞/慢性淋巴细胞白血病2和Ras相关蛋白的抑制。我们的研究结果表明,MC提取物通过调节PAX3抑制肿瘤存活基因,从而改善黑色素瘤的增殖和侵袭。