Objective:Despite the combination of Scutellaria barbata D.Don and Scleromitrion diffusum(Willd.)R.J.Wang(SB-SD)being a recognized Chinese medicinal herbal pair that is commonly used in the treatment of ovarian cancer...Objective:Despite the combination of Scutellaria barbata D.Don and Scleromitrion diffusum(Willd.)R.J.Wang(SB-SD)being a recognized Chinese medicinal herbal pair that is commonly used in the treatment of ovarian cancer,there is a poor understanding of their pharmacological mechanisms.This study examines the antitumor properties and potential mechanisms of SB-SD on human ovarian cancer A2780 cells through a multi-omics approach,establishing a pharmacological basis for clinical utilization.Methods:A range of mass ratios and reagents were used in the hot reflux extraction of SB-SD.The inhibitory effect of the SB-SD extracts on A2780 cell proliferation was assessed using the cell-counting kit 8assay.A zebrafish tumor implantation model was used to evaluate the effects of SB-SD extracts on tumor growth and metastasis in vivo.Transcriptomics and proteomics were used to investigate alterations in biological pathways in A2780 cells after treatment with different concentrations of SB-SD extract.Cell cycle,cell apoptosis,intracellular free iron concentration,intracellular reactive oxygen species(ROS)concentration,malondialdehyde(MDA),and mitochondrial membrane potential were measured.Real-time quantitative reverse transcription polymerase chain reaction and Western blotting were utilized to investigate the effects of heme catabolism and ferritinophagy on ferroptosis induced by SB-SD extract in A2780 cells.Results:The 70%ethanol extract of SB-SD(a mass ratio of 4:1)inhibited A2780 cell proliferation significantly with a half maximal inhibitory concentration of 660μg/m L in a concentration-and timedependent manner.Moreover,it effectively suppressed tumor growth and metastasis in a zebrafish tumor implantation model.SB-SD extract induced the accumulation of free iron,ROS,MDA,and mitochondrial damage in A2780 cells.The mechanisms might involve the upregulated expression of ferritinophagyrelated genes microtubule-associated protein 1 light chain 3,autophagy-related gene 5,and nuclear receptor coactivator 4.Conclusion:SB-SD extract effectively inhibited the development of ovarian cancer both in vitro and in vivo.Its mechanism of action involved inducing ferroptosis by facilitating heme catabolism and ferritinophagy.This herbal pair holds promise as a potential therapeutic option for ovarian cancer treatment and may be utilized in combination with routine treatment to improve the treatment outcomes of ovarian cancer patients.展开更多
基金supported by the National Natural Science Foundation of China(No.81873195)the Applied Basic Research Program of Liaoning Province(No.2023JH2/101300103)+1 种基金the Liaoning Revitalization Talents Program(No.XLYC1907113)the Dalian Medical University Foundation for Teaching Reform Project of Undergraduate Innovative Talents Training(No.111807010303)。
文摘Objective:Despite the combination of Scutellaria barbata D.Don and Scleromitrion diffusum(Willd.)R.J.Wang(SB-SD)being a recognized Chinese medicinal herbal pair that is commonly used in the treatment of ovarian cancer,there is a poor understanding of their pharmacological mechanisms.This study examines the antitumor properties and potential mechanisms of SB-SD on human ovarian cancer A2780 cells through a multi-omics approach,establishing a pharmacological basis for clinical utilization.Methods:A range of mass ratios and reagents were used in the hot reflux extraction of SB-SD.The inhibitory effect of the SB-SD extracts on A2780 cell proliferation was assessed using the cell-counting kit 8assay.A zebrafish tumor implantation model was used to evaluate the effects of SB-SD extracts on tumor growth and metastasis in vivo.Transcriptomics and proteomics were used to investigate alterations in biological pathways in A2780 cells after treatment with different concentrations of SB-SD extract.Cell cycle,cell apoptosis,intracellular free iron concentration,intracellular reactive oxygen species(ROS)concentration,malondialdehyde(MDA),and mitochondrial membrane potential were measured.Real-time quantitative reverse transcription polymerase chain reaction and Western blotting were utilized to investigate the effects of heme catabolism and ferritinophagy on ferroptosis induced by SB-SD extract in A2780 cells.Results:The 70%ethanol extract of SB-SD(a mass ratio of 4:1)inhibited A2780 cell proliferation significantly with a half maximal inhibitory concentration of 660μg/m L in a concentration-and timedependent manner.Moreover,it effectively suppressed tumor growth and metastasis in a zebrafish tumor implantation model.SB-SD extract induced the accumulation of free iron,ROS,MDA,and mitochondrial damage in A2780 cells.The mechanisms might involve the upregulated expression of ferritinophagyrelated genes microtubule-associated protein 1 light chain 3,autophagy-related gene 5,and nuclear receptor coactivator 4.Conclusion:SB-SD extract effectively inhibited the development of ovarian cancer both in vitro and in vivo.Its mechanism of action involved inducing ferroptosis by facilitating heme catabolism and ferritinophagy.This herbal pair holds promise as a potential therapeutic option for ovarian cancer treatment and may be utilized in combination with routine treatment to improve the treatment outcomes of ovarian cancer patients.
