T-粘连蛋白(CDH13)在黑色素瘤加西诺治疗方案中的作用

Cancers Pub Date : 2024-05-12 DOI:10.3390/cancers16101853
Sebastian Staebler, Sebastian Hoechst, Aranya Thongmao, Nadja Schneider, Anja K. Bosserhoff, S. Kuphal
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引用次数: 0

摘要

化疗药物的靶向疗法和检查点抑制剂的免疫疗法是临床医生治疗黑色素瘤指南中推荐的系统疗法之一。虽然黑色素瘤的治疗方法在不断改进,但对既有疗法的耐药性仍时有发生。因此,本研究的目的是探索加西诺对特定癌症特性(如增殖和凋亡)的作用。加西诺是从山竹(Garcinia mangostana)植物中分离出来的一种天然化合物,是一种新发现的癌症治疗方法。许多药物物质都是从植物中提取的。例如,从喜树(Camptotheca acuminate)树皮中提取的喜树碱衍生物,或从西洋紫杉(Taxus brevifolia)树皮中提取的紫杉醇,都被用作抗癌药物。在这里,我们发现加西诺可以减少黑色素瘤细胞株的增殖并诱导其凋亡。此外,我们还发现,细胞-细胞粘附分子 T-cadherin(CDH13)表达阳性的细胞对加西醇的治疗反应更敏感。在使用针对T-cadherin的siRNA池进行基因敲除实验后,细胞对加西诺的敏感性降低,并恢复了增殖和抗凋亡行为。我们的结论是,T-cadherin阳性的患者尤其可以从使用加西诺的治疗中获益。
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The Role of T-Cadherin (CDH13) in Treatment Options with Garcinol in Melanoma
Targeted therapies with chemotherapeutic agents and immunotherapy with checkpoint inhibitors are among the systemic therapies recommended in the guidelines for clinicians to treat melanoma. Although there have been constant improvements in the treatment of melanoma, resistance to the established therapies continues to occur. Therefore, the purpose of this study was to explore the function of garcinol with regards to specific cancer properties such as proliferation and apoptosis. Garcinol, a natural compound isolated from the plant also known as mangosteen (Garcinia mangostana), is a newly discovered option for cancer treatment. Numerous pharmaceutical substances are derived from plants. For example, the derivates of camptothecin, extracted from the bark of the Chinese tree of happiness (Camptotheca acuminate), or paclitaxel, extracted from the bark of the Western yew tree (Taxus brevifolia), are used as anti-cancer drugs. Here, we show that garcinol reduced proliferation and induced apoptosis in melanoma cell lines. In addition, we found that those cells that are positive for the expression of the cell–cell adhesion molecule T-cadherin (CDH13) respond more sensitively to treatment with garcinol. After knock-down experiments with an siRNA pool against T-cadherin, the sensitivity to garcinol decreased and proliferation and anti-apoptotic behavior of the cells was restored. We conclude that patients who are T-cadherin-positive could especially benefit from a therapy with garcinol.
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