Ovarian cancer poses a significant threat to women's health,necessitating effective therapeutic strategies.Emd-D,an emodin derivative,demonstrates enhanced pharmaceutical properties and bioavailability.In this stu...Ovarian cancer poses a significant threat to women's health,necessitating effective therapeutic strategies.Emd-D,an emodin derivative,demonstrates enhanced pharmaceutical properties and bioavailability.In this study,Cell Counting Kit 8(CCK8)assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D.Migration and invasion experiments confirmed its inhibitory effects on OVHM cells,while flow cytometry analysis demonstrated Emd-D-induced apoptosis.Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4.This was corroborated by alterations in intracellular lactate and pyruvate levels,as well as glucose transporter 1(GLUT1)and hexokinase 2(HK2)expression.PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis.In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment,accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors.In conclusion,our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis.These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.展开更多
基金funded by the Natural Science Foundation of Heilongjiang Province(No.LH2023H012)Postdoctoral Research Initiation Fund(No.LBH-Q20152)CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-078)。
文摘Ovarian cancer poses a significant threat to women's health,necessitating effective therapeutic strategies.Emd-D,an emodin derivative,demonstrates enhanced pharmaceutical properties and bioavailability.In this study,Cell Counting Kit 8(CCK8)assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D.Migration and invasion experiments confirmed its inhibitory effects on OVHM cells,while flow cytometry analysis demonstrated Emd-D-induced apoptosis.Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4.This was corroborated by alterations in intracellular lactate and pyruvate levels,as well as glucose transporter 1(GLUT1)and hexokinase 2(HK2)expression.PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis.In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment,accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors.In conclusion,our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis.These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.
