Objective To observe the effects of Centipede Scolopendra extraction(CSE)on human liver cancer HepG2 cells and the nude mouse tumor model of liver orthotopic transplantation,and to explore the anti-liver cancer mechan...Objective To observe the effects of Centipede Scolopendra extraction(CSE)on human liver cancer HepG2 cells and the nude mouse tumor model of liver orthotopic transplantation,and to explore the anti-liver cancer mechanism of the extract.Methods HepG2 cells were respectively treated with CSE250(250μg/mL),CSE500(500μg/mL)and 5-FU,and control group was established.An enzymatic hydrolysis and acetone precipitation method was used to separate and purify CSE,which was then used to treat HepG2 cells.The CCK8 assay was used to detect the inhibition of cell proliferation and the half maximal inhibitory concentration(IC50)was calculated.Flow cytometry was used to analyze the cell cycle,and western blot was used to detect the expression of signal transduction and activator of transcription 3(STAT3)pathway-related proteins in HepG2 cells treated with CSE.A nude mouse model with an orthotopic liver tumor was prepared.The mice were randomly divided into four groups,each containing 12 animals:the model group,the 5-FU group,the CSE10 group[10 mg/(kg·d)]and the CSE50 group[50 mg/(kg·d)].The volume and mass changes in the nude mice with orthotopic transplanted tumors were observed.Western blot method was used to test the protein expression levels of p-STAT3 and p38 mitogen-activated protein kinase(p38MAPK).Tissues from the liver of mice in the model group and the CSE50 group were analyzed by using a protein tyrosine kinase(PTK)chip,and the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)function enrichment analysis of the differentially expressed proteins was performed.Results This study showed that CSE significantly inhibited the proliferation of HepG2 cells(P<0.05).After 48 h of CSE treatment,the cell cycle of HepG2 cells manifested as S phase and G2/M phase;p-STAT3 protein levels in the CSE groups were significantly lower than that in the control group(P<0.05).Analysis of the tumor inhibition in the mice showed that the tumor masses and volume in CSE groups were lower(P<0.05).The protein levels of p-STAT3 and p38MAPK in CSE50 group and 5-FU group decreased significantly(P<0.05).PTK antibody chip screening results showed that CSE groups had a bidirectional regulation trend,and there were 23 up-regulated PTKs and six down-regulated PTKs.The GO and KEGG analyses showed that CSE exerted its anticancer effects through regulation of biological processes,including mitogen-activated protein kinase(MAPK)cascade,chemotaxis,cell invasion,cell adhesion,angiogenesis and other biological processes,and through signaling pathways,including the MAPK,phosphatidylinositol-3-kinase/serine threonine protein kinase(PI3K/AKT),and RAS signaling pathways.Conclusions CSE can effectively inhibite the proliferation of HepG2 cells and effectively inhibite the growth of liver cancer orthotopic transplantation tumor.Its mechanism may be closely related to the regulation of STAT3,MAPK and PI3K/AKT signaling pathways.展开更多
The discovery of novel antitumor agents derived from natural plants is a principal objective of anticancer drug research.Frankincense,a widely recognized natural antitumor medicine,has undergone a systematic review en...The discovery of novel antitumor agents derived from natural plants is a principal objective of anticancer drug research.Frankincense,a widely recognized natural antitumor medicine,has undergone a systematic review encompassing its species,chemical constituents,and diverse pharmacological activities and mechanisms.The different species of frankincense include Boswellia serrata,Somali frankincense,Boswellia frereana,and Boswellia arabica.Various frankincense extracts and compounds exhibit antitumor,anti-inflammatory,and hepatoprotective properties and antioxidation,memory enhancement,and immunological regulation capabilities.They also have comprehensive effects on regulating flora.Frankincense and its principal chemical constituents have demonstrated promising chemoprophylactic and therapeutic abilities against tumors.This review provides a systematic summary of the mechanism of action underlying the antitumor effects of frankincense and its major constituents,thus laying the foundations for developing effective tumor-combating targets.展开更多
基金funding support from the National Natural Science Foundation of China(No.81473617)the Science and Technology Department of Hunan Province(No.2017SK50310)the Hunan Education Department’s Science&Research Project(No.16K066)。
文摘Objective To observe the effects of Centipede Scolopendra extraction(CSE)on human liver cancer HepG2 cells and the nude mouse tumor model of liver orthotopic transplantation,and to explore the anti-liver cancer mechanism of the extract.Methods HepG2 cells were respectively treated with CSE250(250μg/mL),CSE500(500μg/mL)and 5-FU,and control group was established.An enzymatic hydrolysis and acetone precipitation method was used to separate and purify CSE,which was then used to treat HepG2 cells.The CCK8 assay was used to detect the inhibition of cell proliferation and the half maximal inhibitory concentration(IC50)was calculated.Flow cytometry was used to analyze the cell cycle,and western blot was used to detect the expression of signal transduction and activator of transcription 3(STAT3)pathway-related proteins in HepG2 cells treated with CSE.A nude mouse model with an orthotopic liver tumor was prepared.The mice were randomly divided into four groups,each containing 12 animals:the model group,the 5-FU group,the CSE10 group[10 mg/(kg·d)]and the CSE50 group[50 mg/(kg·d)].The volume and mass changes in the nude mice with orthotopic transplanted tumors were observed.Western blot method was used to test the protein expression levels of p-STAT3 and p38 mitogen-activated protein kinase(p38MAPK).Tissues from the liver of mice in the model group and the CSE50 group were analyzed by using a protein tyrosine kinase(PTK)chip,and the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)function enrichment analysis of the differentially expressed proteins was performed.Results This study showed that CSE significantly inhibited the proliferation of HepG2 cells(P<0.05).After 48 h of CSE treatment,the cell cycle of HepG2 cells manifested as S phase and G2/M phase;p-STAT3 protein levels in the CSE groups were significantly lower than that in the control group(P<0.05).Analysis of the tumor inhibition in the mice showed that the tumor masses and volume in CSE groups were lower(P<0.05).The protein levels of p-STAT3 and p38MAPK in CSE50 group and 5-FU group decreased significantly(P<0.05).PTK antibody chip screening results showed that CSE groups had a bidirectional regulation trend,and there were 23 up-regulated PTKs and six down-regulated PTKs.The GO and KEGG analyses showed that CSE exerted its anticancer effects through regulation of biological processes,including mitogen-activated protein kinase(MAPK)cascade,chemotaxis,cell invasion,cell adhesion,angiogenesis and other biological processes,and through signaling pathways,including the MAPK,phosphatidylinositol-3-kinase/serine threonine protein kinase(PI3K/AKT),and RAS signaling pathways.Conclusions CSE can effectively inhibite the proliferation of HepG2 cells and effectively inhibite the growth of liver cancer orthotopic transplantation tumor.Its mechanism may be closely related to the regulation of STAT3,MAPK and PI3K/AKT signaling pathways.
基金Supported by the Youth Project of National Natural Science Foundation of China(No.82104861)National Natural Science Foundation of China(Nos.U20A20408 and 82074450)+1 种基金Natural Science Foundation of Hunan Province of China(Nos.2021JJ40408,2021JJ40420)Hunan Provincial Department of Education General Project(No.20C1407)。
文摘The discovery of novel antitumor agents derived from natural plants is a principal objective of anticancer drug research.Frankincense,a widely recognized natural antitumor medicine,has undergone a systematic review encompassing its species,chemical constituents,and diverse pharmacological activities and mechanisms.The different species of frankincense include Boswellia serrata,Somali frankincense,Boswellia frereana,and Boswellia arabica.Various frankincense extracts and compounds exhibit antitumor,anti-inflammatory,and hepatoprotective properties and antioxidation,memory enhancement,and immunological regulation capabilities.They also have comprehensive effects on regulating flora.Frankincense and its principal chemical constituents have demonstrated promising chemoprophylactic and therapeutic abilities against tumors.This review provides a systematic summary of the mechanism of action underlying the antitumor effects of frankincense and its major constituents,thus laying the foundations for developing effective tumor-combating targets.
