Various therapeutic strategies have been developed to overcome ovarian cancer.However,the prognoses resulting from these strategies are still unclear.In the present work,we screened 54 small molecule compounds approve...Various therapeutic strategies have been developed to overcome ovarian cancer.However,the prognoses resulting from these strategies are still unclear.In the present work,we screened 54 small molecule compounds approved by the FDA to identify novel agents that could inhibit the viability of human epithelial ovarian cancer cells.Among these,we identified disulfiram(DSF),an old alcohol-abuse drug,as a potential inducer of cell death in ovarian cancer.Mechanistically,DSF treatment significantly reduced the expression of the anti-apoptosis marker Bcell lymphoma/leukemia-2(Bcl-2)and increase the expression of the apoptotic molecules Bcl2 associated X(Bax)and cleaved caspase-3 to promote human epithelial ovarian cancer cell apoptosis.Furthermore,DSF is a newly identified effective copper ionophore,thus the combination of DSF and copper was used to reduce ovarian cancer viability than DSF single treatment.Combination treatment with DSF and copper also led to the reduced expression of ferredoxin 1 and loss of Fe-S cluster proteins(biomarkers of cuproptosis).In vivo,DSF and copper gluconate significantly decreased the tumor volume and increased the survival rate in a murine ovarian cancer xenograft model.Thus,the role of DSF revealed its potential for used as a viable therapeutic agent for the ovarian cancer.展开更多
Objective: The aim of the study was to investigate the effect of Casticin (CAS) combination with Cisplatin (DDP) in sub-toxic concentration on apoptosis of human ovarian cancer HO-8910 cells in vitro and unravel the a...Objective: The aim of the study was to investigate the effect of Casticin (CAS) combination with Cisplatin (DDP) in sub-toxic concentration on apoptosis of human ovarian cancer HO-8910 cells in vitro and unravel the associated mechanisms. Methods: Human ovarian cancer HO-8910 cells were cultured in vitro. The inhibitory effect of CAS combination with DDP in sub-toxic concentration on viability of human ovarian cancer HO-8910 cells was evaluated by the MTT assay. Morphological changes of cell apoptosis were detected by Hoechst 33258 staining assay. Cell apoptosis rate was analyzed by flow cytometry. The protein expression level was analyzed by Western blot. Results: CAS in sub-toxic concentration and DDP in sub-toxic concentration could slightly inhibit Human ovarian cancer HO-8910 cells, but CAS combination with DDP in sub-toxic concentration significantly inhibited the growth of HO-8910 cells, and growth inhibition rate was increased drastically compared with the control group (P﹤0.01), and the inhibiting effect showed synergistic action. Human ovarian cancer HO-8910 cells showed the typical morphological changes of apoptosis and apoptosis rate markedly increased when they were exposed to CAS combination with DDP in sub-toxic concentration for 48 h. Western blot showed that the expression of bcl-2 protein was down-regulated and protein level of caspase-3 was activated by CAS combination with DDP in sub-toxic concentration. Conclusion: CAS combination with DDP in sub-toxic concentration could inhibit the cells growth and lead to cell apoptosis in human ovarian cancer HO-8910 cells. And the down-regulation of bcl-2 protein expression and activation of caspase-3 protein might contribute to CAS combination with DDP in sub-toxic concentration in human cancer HO-8910 cells.展开更多
Objective： The aim of the study was to investigate the possible mechanism of induction apoptosis of Onychin （ONY） in ovarian cancer HO-8910 cells in vitro. Methods： Human ovarian cancer HO-8910 cells were cultured...Objective： The aim of the study was to investigate the possible mechanism of induction apoptosis of Onychin （ONY） in ovarian cancer HO-8910 cells in vitro. Methods： Human ovarian cancer HO-8910 cells were cultured in vitro. Inhibi- tory effect of ONY on the viability of HO-8910 cells was evaluated by the MTT assay. Apoptosis of HO-8910 cells treated with different concentrations of ONY for 48 h was detected by FCM. Expression of proteins related to apoptosis was analyzed by Western blot. Results： ONY significantly inhibited the viability of human ovarian cancer HO-8910 cells in a dose-dependent and time-dependent manner, and the ICso was 10.48 pg/mL for 48 h. The cells treated with ONY showed typical morphological change of apoptosis and increased cells of sub-G1 population by FCM in a dose-dependent. Western blot showed that ex- pression of Bax, cytochrome C, caspase-9 and caspase-3 proteins were upregulated and protein level of Bcl-2 was depressed after treatment with ONY in a concentration dependent. Conclusion： Apoptosis of ovarian cancer HO-8910 cells was induced by ONY through mitochondrial apoptosis pathway in vitro.展开更多
Objective： The aim of the study was to investigate the effect of SG1-1776 combination with DDP in sub-toxic concentration on induction of apoptosis of human ovarian cancer HO-8910 ceiis in vitro and to unravei the as...Objective： The aim of the study was to investigate the effect of SG1-1776 combination with DDP in sub-toxic concentration on induction of apoptosis of human ovarian cancer HO-8910 ceiis in vitro and to unravei the associated mechanisms. Methods： Human ovarian cancer HO-8910 cells were cultured in vitro. The inhibitory effect of SG1-1776 combination with DDP in sub-toxic concentration on induction on viability of human ovarian cancer HO-8910 cells was evaiuated by the MTT assay. Cell apoptosis rate was analyzed by flow cytometry. The proteins expression level related to apoptosis were analyzed by Western blot. Results： SG1-1776 combination with DDP in sub-toxic concentration significantiy inhibited the proliferation of human ovarian cancer HO-8910 cells, and proliferation inhibition rate was increased drastically compared with normai saline （NS） group or DDP group in sub-toxic concentration or SG1-1776 group in sub-toxic concentration （P 〈 0.01）. Apoptosis rate markedly increased after the treatment of SG1-1776 combination with DDP in sub-toxic concentration for 48 h. Western blot showed that the expression of bcl-2 protein was down-regulated and protein level of Bax and Cyto-c were depressed by SG1-1776 combination with DDP in sub-toxic concentration. Cenclusion： SG1-1776 combination with DDP in sub-toxic concentration could inhibit the cell proliferation and lead to cell apoptosis inhuman ovarian cancer HO-8910 cells, and its mechanism may be related to through mitochondrial apoptotic pathway.展开更多
The purpose of this study was to investigate the effect of Laggera alata flavonen （LAF） on the inhibit- ing effect of human ovarian cancer HO-8910 cells proliferation and its possible mechanism in vitro. Methods： H...The purpose of this study was to investigate the effect of Laggera alata flavonen （LAF） on the inhibit- ing effect of human ovarian cancer HO-8910 cells proliferation and its possible mechanism in vitro. Methods： Human ovarian cancer HO-8910 cells were cultured in vitro. Inhibitory effect of LAF on the viability of HO-8910 cells was evaluated by the MTT assay. Apoptotic effect of different concentrations of LAF on HO-8910 cells was assessed by AO/EB staining and FCM with propidium iodide （PI） staining. Expression of proteins related to apoptosis was analyzed by Western blot. Results： LAF significantly inhibited the viability of HO-8910 cells proliferation in a dose-dependent and time-dependent manner, there were statistical significance compared with NS group （P 〈 0.05）, and the ICso was 4.28 pg/mL for 48 h. The cells treated with LAF showed typical morphological change and apoptotic rate increased by FCM in a dose-dependent, and there was notable dif- ference compared with NS group （P 〈 0.05）. Western blot showed that expression of Fas, caspase-8, tBid and Cyto-c proteins were up-regulated after treatment with LAF for 48 h in a concentration dependent. Conclusion： LAF could inhibit HO-8910 cells proliferation and induce apoptosis, which may be through the pathway of death receptor in vitro.展开更多
基金funded by Guangzhou Scienceand Information Bureau Item of China(Grant No.201904010013)by Natural Science Foundation of Guangdong Province of China(Grant No.2018A0303130180).
文摘Various therapeutic strategies have been developed to overcome ovarian cancer.However,the prognoses resulting from these strategies are still unclear.In the present work,we screened 54 small molecule compounds approved by the FDA to identify novel agents that could inhibit the viability of human epithelial ovarian cancer cells.Among these,we identified disulfiram(DSF),an old alcohol-abuse drug,as a potential inducer of cell death in ovarian cancer.Mechanistically,DSF treatment significantly reduced the expression of the anti-apoptosis marker Bcell lymphoma/leukemia-2(Bcl-2)and increase the expression of the apoptotic molecules Bcl2 associated X(Bax)and cleaved caspase-3 to promote human epithelial ovarian cancer cell apoptosis.Furthermore,DSF is a newly identified effective copper ionophore,thus the combination of DSF and copper was used to reduce ovarian cancer viability than DSF single treatment.Combination treatment with DSF and copper also led to the reduced expression of ferredoxin 1 and loss of Fe-S cluster proteins(biomarkers of cuproptosis).In vivo,DSF and copper gluconate significantly decreased the tumor volume and increased the survival rate in a murine ovarian cancer xenograft model.Thus,the role of DSF revealed its potential for used as a viable therapeutic agent for the ovarian cancer.
基金Supported by a grant from the Hunan Provincial Education Department(No.2011.91.11C1109)
文摘Objective: The aim of the study was to investigate the effect of Casticin (CAS) combination with Cisplatin (DDP) in sub-toxic concentration on apoptosis of human ovarian cancer HO-8910 cells in vitro and unravel the associated mechanisms. Methods: Human ovarian cancer HO-8910 cells were cultured in vitro. The inhibitory effect of CAS combination with DDP in sub-toxic concentration on viability of human ovarian cancer HO-8910 cells was evaluated by the MTT assay. Morphological changes of cell apoptosis were detected by Hoechst 33258 staining assay. Cell apoptosis rate was analyzed by flow cytometry. The protein expression level was analyzed by Western blot. Results: CAS in sub-toxic concentration and DDP in sub-toxic concentration could slightly inhibit Human ovarian cancer HO-8910 cells, but CAS combination with DDP in sub-toxic concentration significantly inhibited the growth of HO-8910 cells, and growth inhibition rate was increased drastically compared with the control group (P﹤0.01), and the inhibiting effect showed synergistic action. Human ovarian cancer HO-8910 cells showed the typical morphological changes of apoptosis and apoptosis rate markedly increased when they were exposed to CAS combination with DDP in sub-toxic concentration for 48 h. Western blot showed that the expression of bcl-2 protein was down-regulated and protein level of caspase-3 was activated by CAS combination with DDP in sub-toxic concentration. Conclusion: CAS combination with DDP in sub-toxic concentration could inhibit the cells growth and lead to cell apoptosis in human ovarian cancer HO-8910 cells. And the down-regulation of bcl-2 protein expression and activation of caspase-3 protein might contribute to CAS combination with DDP in sub-toxic concentration in human cancer HO-8910 cells.
文摘Objective： The aim of the study was to investigate the possible mechanism of induction apoptosis of Onychin （ONY） in ovarian cancer HO-8910 cells in vitro. Methods： Human ovarian cancer HO-8910 cells were cultured in vitro. Inhibi- tory effect of ONY on the viability of HO-8910 cells was evaluated by the MTT assay. Apoptosis of HO-8910 cells treated with different concentrations of ONY for 48 h was detected by FCM. Expression of proteins related to apoptosis was analyzed by Western blot. Results： ONY significantly inhibited the viability of human ovarian cancer HO-8910 cells in a dose-dependent and time-dependent manner, and the ICso was 10.48 pg/mL for 48 h. The cells treated with ONY showed typical morphological change of apoptosis and increased cells of sub-G1 population by FCM in a dose-dependent. Western blot showed that ex- pression of Bax, cytochrome C, caspase-9 and caspase-3 proteins were upregulated and protein level of Bcl-2 was depressed after treatment with ONY in a concentration dependent. Conclusion： Apoptosis of ovarian cancer HO-8910 cells was induced by ONY through mitochondrial apoptosis pathway in vitro.
基金Supported by a grant from the Guangzhou Science and Technology Plan Project(No.2013 00000151)
文摘Objective： The aim of the study was to investigate the effect of SG1-1776 combination with DDP in sub-toxic concentration on induction of apoptosis of human ovarian cancer HO-8910 ceiis in vitro and to unravei the associated mechanisms. Methods： Human ovarian cancer HO-8910 cells were cultured in vitro. The inhibitory effect of SG1-1776 combination with DDP in sub-toxic concentration on induction on viability of human ovarian cancer HO-8910 cells was evaiuated by the MTT assay. Cell apoptosis rate was analyzed by flow cytometry. The proteins expression level related to apoptosis were analyzed by Western blot. Results： SG1-1776 combination with DDP in sub-toxic concentration significantiy inhibited the proliferation of human ovarian cancer HO-8910 cells, and proliferation inhibition rate was increased drastically compared with normai saline （NS） group or DDP group in sub-toxic concentration or SG1-1776 group in sub-toxic concentration （P 〈 0.01）. Apoptosis rate markedly increased after the treatment of SG1-1776 combination with DDP in sub-toxic concentration for 48 h. Western blot showed that the expression of bcl-2 protein was down-regulated and protein level of Bax and Cyto-c were depressed by SG1-1776 combination with DDP in sub-toxic concentration. Cenclusion： SG1-1776 combination with DDP in sub-toxic concentration could inhibit the cell proliferation and lead to cell apoptosis inhuman ovarian cancer HO-8910 cells, and its mechanism may be related to through mitochondrial apoptotic pathway.
文摘The purpose of this study was to investigate the effect of Laggera alata flavonen （LAF） on the inhibit- ing effect of human ovarian cancer HO-8910 cells proliferation and its possible mechanism in vitro. Methods： Human ovarian cancer HO-8910 cells were cultured in vitro. Inhibitory effect of LAF on the viability of HO-8910 cells was evaluated by the MTT assay. Apoptotic effect of different concentrations of LAF on HO-8910 cells was assessed by AO/EB staining and FCM with propidium iodide （PI） staining. Expression of proteins related to apoptosis was analyzed by Western blot. Results： LAF significantly inhibited the viability of HO-8910 cells proliferation in a dose-dependent and time-dependent manner, there were statistical significance compared with NS group （P 〈 0.05）, and the ICso was 4.28 pg/mL for 48 h. The cells treated with LAF showed typical morphological change and apoptotic rate increased by FCM in a dose-dependent, and there was notable dif- ference compared with NS group （P 〈 0.05）. Western blot showed that expression of Fas, caspase-8, tBid and Cyto-c proteins were up-regulated after treatment with LAF for 48 h in a concentration dependent. Conclusion： LAF could inhibit HO-8910 cells proliferation and induce apoptosis, which may be through the pathway of death receptor in vitro.
