Kantapan Jiraporn, Intachai Nuttawadee, Khamto Nopawit, Meepowpan Puttinan, Sangthong Padchanee, Wantanajittikul Kittichai, Dechsupa Nathupakorn, Chitapanarux Imjai
Molecular Imaging and Therapy Research Unit, Department Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
Department Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
Pharmaceuticals (Basel). 2022 Jul 4;15(7):830. doi: 10.3390/ph15070830.
Although cisplatin is a first-line chemotherapy drug for head and neck squamous cell carcinoma (HNSCC), its therapeutic efficacy is limited owing to serious side effects and acquired drug resistance. This study determined whether combining pentagalloyl glucose (PGG) and cisplatin enhanced their anti-tumor activities on HNSCC cell lines. We investigated the anticancer effect of PGG combined with cisplatin in 2D and 3D multicellular spheroid cell culture. The results revealed that PGG combined with cisplatin inhibited cell viability and produced synergistic effects. PGG potentiates the anticancer effect of cisplatin by promoting apoptosis and inhibiting cell migration. The western blot and molecular docking analysis revealed that the synergistic effect of the combination treatment may be related to the PGG-mediated reduced expression of phosphorylated STAT3 and phosphorylated Akt. Furthermore, we found that the combined treatment of PGG and cisplatin's effect on 3D multicellular spheroid size was more potent than the monotherapies. Our findings indicated that the combination therapy of PGG and cisplatin synergistically inhibited HNSCC cancer cell viability and induced apoptosis in 2D and 3D models. The present results suggested that PGG may be a promising adjunct drug used with cisplatin for a practical therapeutic approach to head and neck cancer.
尽管顺铂是头颈部鳞状细胞癌（HNSCC）的一线化疗药物，但其治疗效果因严重的副作用和获得性耐药性而受到限制。本研究确定了五倍子酰葡萄糖（PGG）与顺铂联合使用是否能增强它们对HNSCC细胞系的抗肿瘤活性。我们在二维和三维多细胞球体细胞培养中研究了PGG与顺铂联合使用的抗癌效果。结果显示，PGG与顺铂联合使用可抑制细胞活力并产生协同作用。PGG通过促进细胞凋亡和抑制细胞迁移增强了顺铂的抗癌效果。蛋白质印迹和分子对接分析表明，联合治疗的协同作用可能与PGG介导的磷酸化STAT3和磷酸化Akt表达降低有关。此外，我们发现PGG与顺铂联合治疗对三维多细胞球体大小的影响比单一疗法更有效。我们的研究结果表明，PGG与顺铂联合治疗在二维和三维模型中协同抑制了HNSCC癌细胞活力并诱导了细胞凋亡。目前的结果表明，PGG可能是一种有前景的辅助药物，可与顺铂联合用于头颈癌的实际治疗方法。
