Surgical Department of Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.
Department of Radiology, Asia University Hospital, Taichung, Taiwan, R.O.C.
Anticancer Res. 2020 Dec;40(12):6723-6732. doi: 10.21873/anticanres.14695. Epub 2020 Dec 7.
BACKGROUND/AIM: Nuclear factor kappa B (NF-κB) inactivation and apoptosis activation have been shown to enhance the anticancer effect of cisplatin in oral squamous cell carcinoma (OSCC). Amentoflavone may suppress NF-κB activity and trigger apoptosis in different types of cancer. The aim of this study was to investigate the anticancer effect and mechanism of amentoflavone in combination with cisplatin in OSCC.
We investigated the combination effect and mechanism of amentoflavone and cisplatin via cell viability analysis, flow cytometry-based apoptosis analyses, transwell migration/invasion assay, immunofluorescence staining and western blotting assay.
Both amentoflavone and QNZ (NF-κB inhibitor) significantly increased cisplatin-induced cytotoxicity. Amentoflavone reduced cisplatin-triggered NF-κB activity and enhanced cisplatin-induced intrinsic caspase-dependent and independent apoptotic pathways. Moreover, amentoflavone augments cisplatin-suppressed invasion and migration ability of OSCC cells.
Inactivation of NF-κB and induction of apoptosis through intrinsic caspase-dependent and independent apoptotic pathways are associated with amentoflavone enhanced anti-OSCC efficacy of cisplatin.
背景/目的：核因子 kappa B（NF-κB）失活和细胞凋亡的激活已被证明可增强顺铂在口腔鳞状细胞癌（OSCC）中的抗癌作用。山柰酚可能会抑制不同类型癌症中的 NF-κB 活性并触发细胞凋亡。本研究旨在探讨山柰酚与顺铂联合应用于 OSCC 的抗癌作用及其机制。
我们通过细胞活力分析、基于流式细胞术的细胞凋亡分析、Transwell 迁移/侵袭测定、免疫荧光染色和 Western blot 分析研究了山柰酚和顺铂的联合作用和机制。
山柰酚和 QNZ（NF-κB 抑制剂）均显著增加了顺铂诱导的细胞毒性。山柰酚降低了顺铂触发的 NF-κB 活性，并增强了顺铂诱导的内在半胱天冬酶依赖性和非依赖性细胞凋亡途径。此外，山柰酚增强了顺铂抑制的 OSCC 细胞的侵袭和迁移能力。
通过内在半胱天冬酶依赖性和非依赖性细胞凋亡途径使 NF-κB 失活和诱导细胞凋亡与山柰酚增强顺铂对 OSCC 的抗癌作用有关。
