OBJECTIVE: OC is one of the most common cancers with high mortality in women. The purpose of this study was to find out how ginkgetin inhibited OC and which signal transduction pathways was involved to suppress OC.
METHODS: The OC cell lines, A2780, SK-OV-3 and CP70, were used for in vitro experiments. MTT assay, colony formation, apoptosis assay, scratch wound assay and cell invasion assay were used to determine the inhibitory effect of ginkgetin. BALB/c nude female mice were injected with A2780 cells subcutaneously, then treated with ginkgetin by intragastric administration. Western blot experiment was used to verify the inhibitory mechanism of OC in vitro and in vivo.
RESULTS: We found that ginkgetin inhibited the proliferation and induced apoptosis in OC cells. In addition, ginkgetin reduced migration and invasion of OC cells. In vivo study showed that ginkgetin significantly reduced tumor volume in the xenograft mouse model. Furthermore, the anti-tumor effects of ginkgetin were associated with a down regulation of p-STAT3, p-ERK and SIRT1 both in vitro and in vivo.
CONCLUSIONS: Our results suggest that ginkgetin exhibits anti-tumor activity in OC cells via inhibiting the JAK2/STAT3 and MAPK pathways and SIRT1 protein. Ginkgetin could be a potential candidate for the treatment of OC.
目的:OC是女性最常见的高死亡率癌症之一。这项研究的目的是找出银杏素如何抑制OC以及抑制OC的信号转导途径。
方法:OC细胞系,A2780、SK-OV-3和CP70用于体外实验。MTT测定,菌落形成,凋亡测定,用划痕试验和细胞侵袭试验测定银杏素的抑制作用。BALB/c裸雌性小鼠皮下注射A2780细胞,然后用银杏素灌胃治疗。Westernblot实验用于验证OC的体内外抑制机制。
结果:我们发现银杏素能抑制OC细胞的增殖和诱导凋亡。此外,银杏素减少OC细胞的迁移和侵袭。体内研究表明,在异种移植小鼠模型中,银杏叶素可显着减少肿瘤体积。此外,银杏素的抗肿瘤作用与体内外p-STAT3,p-ERK和SIRT1的下调有关.
结论:我们的结果表明,银杏素通过抑制JAK2/STAT3和MAPK通路以及SIRT1蛋白在OC细胞中具有抗肿瘤活性。银杏素可能是治疗OC的潜在候选药物。