Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Western Yanta Road, Xi'an, 710061, Shaanxi, People's Republic of China.
Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, People's Republic of China.
Cancer Chemother Pharmacol. 2020 Feb;85(2):379-390. doi: 10.1007/s00280-019-03999-9. Epub 2019 Dec 12.
6-Gingerol, a major biochemical and pharmacological active ingredient of ginger, has shown anti-inflammatory and antitumor activities against various cancers. Searching for natural products with fewer side effects for developing adjunctive therapeutic options is necessary.
The effects of 6-gingerol on proliferation, colony formation, and cell cycle in RCC cells were detected by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and propidium iodide (PI) staining, respectively. Western blotting, an immunofluorescence assay, and immunohistochemical staining were performed to assess the expression of relevant proteins. A subcutaneous tumor model was set up to investigate the 6-gingerol effects on tumor growth in vivo, and the pharmacokinetics of 6-gingerol in mice were detected by LC/MS assays.
6-Gingerol treatment exerted time- and dose-dependent inhibition of the growth and colony formation of ACHN, 786-O, and 769-P cells, leading to a concomitant induction of cell-cycle G1-phase arrest and decrease in Ki-67 expression in the cell nucleus. Western-blotting results showed that 6-gingerol reduces phosphorylation of protein kinase B (AKT) Ser 473, cyclin-dependent kinases (CDK4), and cyclin D1 and, meanwhile, increases glycogen synthase kinase (GSK 3β) protein amount. Furthermore, the efficacy of 6-gingerol was demonstrated in an in vivo murine model of 786-O.
The above results indicate that 6-gingerol can induce cell-cycle arrest and cell-growth inhibition through the AKT-GSK 3β-cyclin D1 signaling pathway in vitro and in vivo, suggesting that 6-gingerol should be useful for renal-cell carcinoma treatment.
6-姜酚是生姜的一种主要生化和药理活性成分，已显示出对各种癌症的抗炎和抗肿瘤活性。寻找副作用较少的天然产物来开发辅助治疗方法是必要的。
通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）测定法、集落形成测定法和碘化丙啶（PI）染色法分别检测 6-姜酚对 RCC 细胞增殖、集落形成和细胞周期的影响。采用 Western blot、免疫荧光检测和免疫组织化学染色法检测相关蛋白的表达。建立皮下肿瘤模型，研究 6-姜酚对体内肿瘤生长的影响，并通过 LC/MS 测定法检测 6-姜酚在小鼠体内的药代动力学。
6-姜酚处理对 ACHN、786-O 和 769-P 细胞的生长和集落形成具有时间和剂量依赖性抑制作用，导致细胞周期 G1 期阻滞和核内 Ki-67 表达减少。Western blot 结果表明，6-姜酚降低蛋白激酶 B（AKT）Ser 473、细胞周期蛋白依赖性激酶（CDK4）和细胞周期蛋白 D1 的磷酸化，同时增加糖原合成酶激酶（GSK 3β）蛋白量。此外，6-姜酚在 786-O 的体内小鼠模型中显示出疗效。
上述结果表明，6-姜酚可以通过 AKT-GSK 3β-cyclin D1 信号通路在体外和体内诱导细胞周期阻滞和细胞生长抑制，表明 6-姜酚可用于肾细胞癌的治疗。
