Pentagalloyl Glucose and Cisplatin Combination Treatment Exhibits a Synergistic Anticancer Effect in 2D and 3D Models of Head and Neck Carcinoma

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.