Wei Chunhong, Jiang Peng, Li Guangxu, Li Meng, Wang Li
Department of Oncology, Second People's Hospital of Dezhou, Decheng District, Dezhou, Shandong Province, China.
Department of Endoscopic, Second People's Hospital of Dezhou, Decheng District, Dezhou, Shandong Province, China.
Arch Med Sci. 2021 Apr 13;18(3):753-760. doi: 10.5114/aoms/121038. eCollection 2022.
Gastric cancer is a frequently detected malignancy, and its incidence has increased over the past decades in East Asia. The present study investigated the effect of 5,7,2, 5-tetrahydroxy-8,6-dimethoxyflavone (THDMF) on gastric cancer cells and explored the underlying mechanism. The study analysed cell viability changes, apoptotic features, and metastasis potential of treatment with THDMF.
MTT colorimetric assay was used for measurement of MKN28, MKN45, and GES-1 cell proliferation and flow cytometry for the detection of apoptosis. Transwell and wound healing assays were used to observe the invasion and migration abilities of MKN28 cells. The expression of p21, MMP2/-9, PI3K, and c-Myc proteins was detected by western blotting.
The THDMF treatment significantly ( < 0.05) reduced MKN28 and MKN45 cell proliferation without changing GES-1 cell viability. A significant increase in apoptotic cell population on treatment with THDMF was observed. Treatment of MKN28 cells with THDMF increased the percentage of cells in the G1 phase. Exposure of MKN28 cells to THDMF caused a marked decrease in invasion and migration potential in comparison to control cells. The expression of miR-145 was markedly increased in MKN28 cells on treatment with THDMF. In MKN28 cells expression of c-Myc, PI3K, p-AKT, MMP-2, and MMP-9 was suppressed markedly on exposure to THDMF. The expression of p21 protein in MKN28 cells was markedly promoted on exposure to THDMF.
THDMF exhibits anti-cancer effect on gastric cancer cells by activation of cell apoptosis and arrest of cell cycle. In addition, THDMF promoted miR-145 expression and down-regulation of PI3K/AKT signalling pathway in MKN28 cells. Therefore, THDMF may be utilised as a potential novel therapeutic agent for the treatment of gastric cancer.
胃癌是一种常见的恶性肿瘤，在过去几十年中其发病率在东亚地区有所上升。本研究调查了5,7,2,5 - 四羟基 - 8,6 - 二甲氧基黄酮（THDMF）对胃癌细胞的影响，并探讨了其潜在机制。该研究分析了THDMF处理后的细胞活力变化、凋亡特征和转移潜能。
采用MTT比色法检测MKN28、MKN45和GES - 1细胞的增殖情况，采用流式细胞术检测细胞凋亡。使用Transwell和伤口愈合试验观察MKN28细胞的侵袭和迁移能力。通过蛋白质印迹法检测p21、MMP2 / - 9、PI3K和c - Myc蛋白的表达。
THDMF处理显著（<0.05）降低了MKN28和MKN45细胞的增殖，而不改变GES - 1细胞的活力。观察到THDMF处理后凋亡细胞群体显著增加。用THDMF处理MKN28细胞增加了G1期细胞的百分比。与对照细胞相比，MKN28细胞暴露于THDMF后侵袭和迁移潜能显著降低。用THDMF处理后，MKN28细胞中miR - 145的表达显著增加。在MKN28细胞中，暴露于THDMF后，c - Myc、PI3K、p - AKT、MMP - 2和MMP - 9的表达明显受到抑制。暴露于THDMF后，MKN28细胞中p21蛋白的表达明显升高。
THDMF通过激活细胞凋亡和阻断细胞周期对胃癌细胞表现出抗癌作用。此外，THDMF促进了MKN28细胞中miR - 145的表达并下调了PI3K / AKT信号通路。因此，THDMF可能作为一种潜在的新型治疗药物用于治疗胃癌。
