文献类型：期刊文献

英文题名：Flavonoid-Rich Extract of Oldenlandia diffusa (Willd.) Roxb. Inhibits Gastric Cancer by Activation of Caspase-Dependent Mitochondrial Apoptosis

作者：Ling Jia-yin[1,2];Wang Qiu-lan[1,2];Liang Hao-nan[1,2];Liu Qing-bo[1,2];Yin Dong-hong[1,2];Lin Li[3,4]

第一作者：Ling Jia-yin

通信作者：Wang, QL[1];Wang, QL[2]

机构：[1]Gansu Univ Chinese Med, Sch Clin Med 1, Lanzhou 730000, Peoples R China;[2]Gansu Prov Hosp, Lanzhou 730000, Peoples R China;[3]Gansu Univ Chinese Med, Coll Pharm, Lanzhou 730000, Peoples R China;[4]Gansu Univ Chinese Med, Inst Chinese Tibetan Med Resources, Lanzhou 730000, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Sch Clin Med 1, Lanzhou 730000, Peoples R China;[2]corresponding author), Gansu Prov Hosp, Lanzhou 730000, Peoples R China.|[10735]甘肃中医药大学;

年份：2023

卷号：29

期号：3

起止页码：213

外文期刊名：CHINESE JOURNAL OF INTEGRATIVE MEDICINE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000847985500001)】；

基金：Supported by the Key Research and Development Program of Gansu Province (No. 21YF5FA131), the Innovation Fund of Gansu Universities (No. 2021A-084), and the Graduate Innovation Fund of Gansu University of Chinese Medicine (No. 2021CX49)

语种：英文

外文关键词：Chinese medicine; Oldenlandia diffusa flavonoids; gastric cancer; apoptosis; mitochondria

摘要：Objective To evaluate the apoptosis and cycle arrest effects of Oldenlandia diffusa flavonoids on human gastric cancer cells, determine the action mechanisms in association with the mitochondrial dependent signal transduction pathway that controls production of reactive oxygen species (ROS), and evaluate the pharmacodynamics of a mouse xenotransplantation model to provide a reference for the use of flavonoids in prevention and treatment of gastric cancer. Methods Flavonoids were extracted by an enzymatic-ultrasonic assisted method and purified with D-101 resin. Bioactive components were characterized by high-performance liquid chromatography. Cell lines MKN-45, AGS, and GES-1 were treated with different concentrations of flavonoids (64, 96, 128, 160 mu g/mL). The effect of flavonoids on cell viability was evaluated by MTT method, and cell nuclear morphology was observed by Hoechst staining. The apoptosis rate and cell cycle phases were measured by flow cytometry, the production of ROS was detected by laser confocal microscope, the mitochondrial membrane potential (MMP) were observed by fluorescence microscope, and the expression of apoptotic proteins related to activation of mitochondrial pathway were measured by immunoblotting. MKN-45 cells were transplanted into BALB/c nude mice to establish a xenograft tumor model. Hematoxylin and eosin staining was used to reveal the subcutaneous tumor tissue. The tumor volume and tumor weight were measured, the expression levels of proliferation markers proliferating cell nuclear antigen (PCNA) and Ki-67 were detected by immunohistochemistry, and the expression levels of CA72-4 were measured by enzyme linked immunosorbent assay. Results Oldenlandia diffusa flavonoids inhibited proliferation of MKN-45 and AGS human gastric cancer cells, arrested the cell cycle in G(1)/S phase, induced accumulation of ROS in the process of apoptosis, and altered MMP. In addition, flavonoids increased Apaf-1, Cleaved-Caspase-3, and Bax, and decreased Cyclin A, Cdk2, Bcl-2, Pro-Caspase-9, and Mitochondrial Cytochrome C (P<0.05). The MKN-45 cell mouse xenotransplantation model further clarified the growth inhibitory effect of flavonoids towards tumors. The expression levels of PCNA and Ki-67 decreased in each flavonoid dose group, the expression level of CA72-4 decreased (P<0.05). Conclusion Flavonoids derived from Oldenlandia diffusa can inhibit proliferation and induce apoptosis of human gastric cancer cells by activating the mitochondrial controlled signal transduction pathway.