Department of Traditional Chinese Medicine, Pingtung Veterans General Hospital, Pingtung, Taiwan, R.O.C.
Department of Traditional Chinese Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C.
Anticancer Res. 2023 Sep;43(9):4015-4022. doi: 10.21873/anticanres.16589.
BACKGROUND/AIM: Cisplatin is a drug for treating oral cancer. However, several previous studies indicate that oral cancer cells can develop resistance to cisplatin, which may result in a poor prognosis for patients with oral cancer. Fucoidan, a natural health product extracted from brown seaweed, has anticancer abilities against various types of cancer cell. This study evaluated whether fucoidan can enhance the sensitivity of oral cancer cells to cisplatin and explored the underlying mechanism.
SCC-25 cells were used in the present study and treated with 0.3125 mg/ml fucoidan, 12.5 μg/ml cisplatin, or 0.3125 mg/ml fucoidan plus 12.5 μg/ml cisplatin for 48 h, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, enzyme-linked immunosorbent, and immunoblotting assays were performed to evaluate cell survival, cytokeratin-18 fragment release, and expression of markers of apoptosis and autophagy, respectively.
Cotreatment with fucoidan enhanced cisplatin-induced reduction of SCC-25 cell survival compared to cisplatin alone. In addition, cotreatment also increased the expression of apoptosis markers, including activated caspase-8, activated caspase-9, activated caspase-3, and cleaved poly(ADP-ribose) polymerase (PARP), but did not increase the expression of the two autophagy markers studied, beclin and autophagy-related 12-autophagy-related 5 conjugate. Fucoidan significantly inhibited cisplatin-induced AKT serine/threonine kinase 1 activation, which promoted PARP cleavage, caspase-3 activation, and cytokeratin-18 fragment expression in SCC-25 cells.
Fucoidan promoted cisplatin-induced effects by inhibiting phosphatidylinositol 4,5 bisphosphate 3 kinase/AKT serine/threonine kinase 1 activation induced by cisplatin. The results of this study may provide a basis for the possible application of the combination of fucoidan and cisplatin in the clinical treatment of oral cancer in the future to improve the prognosis of patients with oral cancer.
背景/目的：顺铂是一种治疗口腔癌的药物。然而，几项先前的研究表明，口腔癌细胞可能对顺铂产生耐药性，这可能导致口腔癌患者的预后不佳。褐藻中提取的天然保健品岩藻聚糖具有针对各种类型癌细胞的抗癌能力。本研究评估了岩藻聚糖是否可以提高口腔癌细胞对顺铂的敏感性，并探讨了其潜在机制。
本研究使用 SCC-25 细胞，用 0.3125mg/ml 岩藻聚糖、12.5μg/ml 顺铂或 0.3125mg/ml 岩藻聚糖加 12.5μg/ml 顺铂处理 48 小时，采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐、酶联免疫吸附和免疫印迹试验分别评估细胞存活、细胞角蛋白-18 片段释放以及凋亡和自噬标志物的表达。
与单独使用顺铂相比，岩藻聚糖联合治疗增强了顺铂诱导的 SCC-25 细胞存活率降低。此外，联合治疗还增加了凋亡标志物的表达，包括活化的半胱氨酸蛋白酶-8、活化的半胱氨酸蛋白酶-9、活化的半胱氨酸蛋白酶-3 和裂解多聚（ADP-核糖）聚合酶（PARP），但并未增加所研究的两种自噬标志物，即 beclin 和自噬相关蛋白 12-自噬相关蛋白 5 复合物的表达。岩藻聚糖显著抑制顺铂诱导的丝氨酸/苏氨酸激酶 1 的激活，从而促进了 SCC-25 细胞中 PARP 裂解、半胱氨酸蛋白酶-3 激活和细胞角蛋白-18 片段的表达。
岩藻聚糖通过抑制顺铂诱导的磷脂酰肌醇 4,5 二磷酸 3 激酶/丝氨酸/苏氨酸激酶 1 的激活，促进了顺铂诱导的作用。本研究的结果可能为未来岩藻聚糖和顺铂联合应用于临床治疗口腔癌，改善口腔癌患者预后提供依据。
