Glioblastoma multiforme(GBM)in the central nervous system is the most lethal advanced glioma and currently there is no effective treatment for it.Studies of sinomenine,an alkaloid from the Chinese medicinal plant,Sino...Glioblastoma multiforme(GBM)in the central nervous system is the most lethal advanced glioma and currently there is no effective treatment for it.Studies of sinomenine,an alkaloid from the Chinese medicinal plant,Sinomenium acutum,showed that it had inhibitory effects on several kinds of cancer.Here,we synthesized a sinomenine derivative,sino-wcj-33(SW33),tested it for antitumor activity on GBM and explored the underlying mechanism.SW33 significantly inhibited proliferation and colony formation of GBM and reduced migration and invasion of U87 and U251 cells.It also arrested the cell cycle at G2/M phase and induced mitochondria-dependent apoptosis.Differential gene enrichment analysis and pathway validation showed that SW33 exerted anti-GBM effects by regulating PI3 K/AKT and AMPK signaling pathways and significantly suppressed tumorigenicity with no obvious adverse effects on the body.SW33 also induced autophagy through the PI3 K/AKT/mTOR and AMPK/mTOR pathways.Thus,SW33 appears to be a promising drug for treating GBM effectively and safely.展开更多
As a cell cycle regulator, the Myb-related CDC5 protein was reported to be essential for the G2 phase of the cell cycle in yeast and animals, but little is known about its function in plants. Here we report the functi...As a cell cycle regulator, the Myb-related CDC5 protein was reported to be essential for the G2 phase of the cell cycle in yeast and animals, but little is known about its function in plants. Here we report the functional characterization of the CDC5 gene in Arabidopsis thaliana. Arabidopsis CDC5 （AtCDC5） is mainly expressed in tissues with high cell division activity, and is expressed throughout the entire process of embryo formation. The AtCDC5 loss-of-function mutant is embryonic lethal. In order to investigate the function of AtCDC5 in vivo, we generated AtCDC5-RNAi plants in which the expression of AtCDC5 was reduced by RNA interference. We found that the G2 to M （G2/M） phase transition was affected in the AtCDC5-RNAi plants, and that endoreduplication was increased. Additionally, the maintenance of shoot apical meristem （SAM） function was disturbed in the AtCDC5-RNAi plants, in which both the WUSCHEL （WUS）- CLAVATA （CLV） and the SHOOT MERISTEMLESS （STM） pathways were impaired. In situ hybridization analysis showed that the expression of STMwas greatly reduced in the shoot apical cells of the AtCDC5-RNAi plants. Moreover, cyclinB1 or Histone4 was found to be expressed in some of these cells when the transcript of STM was undetectable. These results suggest that AtCDC5 is essential for the G2/M phase transition and may regulate the function of SAM by controlling the expression ofSTMand WUS.展开更多
Objective:To identify the influence on radiosensitivity of lung glandular cancer cells when excisions repair cross-complementing group1(ERCC1) gene was silenced by targeted siR NA.Methods:siR NA which targeting to ERC...Objective:To identify the influence on radiosensitivity of lung glandular cancer cells when excisions repair cross-complementing group1(ERCC1) gene was silenced by targeted siR NA.Methods:siR NA which targeting to ERCC1 and control siR NA was designed and synthesized.The human lung glandular cancer SPC-A-1 cells was transfected.A total of 56 nude mice were divided into two groups,and two kinds of SPC-A-1 cells were transplanted to armpit of right forelimb,to establish the nude mice subcutaneous xenotransplanted tumor model of human lung glandular cancer cells.After the tumor was developed,the nude mice were randomly divided into four groups and accepted different doses of X-Ray radiation,then the change of tumor volume,survival time of mice in every group were recorded and the average lifetime was calculated.Twenty-one days later of X-ray experiment,two mice were taken and sacrificed in each group and the tumors organizations were stripped.The cell apoptosis rate and cell cycle distributions were obtained by FCM(flow cytometry).Results:The volume of tumor which ERCC1 gene was silenced was less than single irradiation group after X-ray irradiation,and the growth speed was slower and the lifetime of mice was lengthened as well(P<0.05).The cells apoptosis rate and the rate of G2/M cells which ERCC1 gene was silenced were higher than the same dose control group and the rate of G_1 cells were lower,which indicated that the cells could be stopped at G_2/M point,the cell proliferation was inhibited,the cell apoptosis was promoted and the radiation sensitivity was improved after the ERCC1 was silenced.Conclusions:The radiation sensitivity of lung glandular tumor could be improved after the ERCC1 gene was silenced by siR NA.展开更多
基金funded by Beijing Natural Science Foundation(7212157,China)CAMS Innovation Fund for Medical Sciences(2016-I2M-3-007,China)+1 种基金National Natural Science Foundation of China(81703536,81803584,81703565,China)Science and Technology Major Projects for“Major New Drugs Innovation and Development”(2018ZX09711001-005-025,2018ZX09711001012,China)。
文摘Glioblastoma multiforme(GBM)in the central nervous system is the most lethal advanced glioma and currently there is no effective treatment for it.Studies of sinomenine,an alkaloid from the Chinese medicinal plant,Sinomenium acutum,showed that it had inhibitory effects on several kinds of cancer.Here,we synthesized a sinomenine derivative,sino-wcj-33(SW33),tested it for antitumor activity on GBM and explored the underlying mechanism.SW33 significantly inhibited proliferation and colony formation of GBM and reduced migration and invasion of U87 and U251 cells.It also arrested the cell cycle at G2/M phase and induced mitochondria-dependent apoptosis.Differential gene enrichment analysis and pathway validation showed that SW33 exerted anti-GBM effects by regulating PI3 K/AKT and AMPK signaling pathways and significantly suppressed tumorigenicity with no obvious adverse effects on the body.SW33 also induced autophagy through the PI3 K/AKT/mTOR and AMPK/mTOR pathways.Thus,SW33 appears to be a promising drug for treating GBM effectively and safely.
基金Acknowledgments The authors thank Dr Liying Du （Peking University, China） for technical help on the flow cytometric analysis. The authors also thank Dr Zhongchi Liu （University of Maryland, USA）, Dr Chun-Ming Liu （Institute of Botany CAS, China）, Dr Terry Matthew （University of Southampton, UK）, Professor Daochun Kong （Peking University, China） and Dr Naomi Nakayama （Yale University, USA） for critical comments and valuable discussion. This work was supported by the National Natural Science Foundation of China （GN 30625002 to L-J Qu）.
文摘As a cell cycle regulator, the Myb-related CDC5 protein was reported to be essential for the G2 phase of the cell cycle in yeast and animals, but little is known about its function in plants. Here we report the functional characterization of the CDC5 gene in Arabidopsis thaliana. Arabidopsis CDC5 （AtCDC5） is mainly expressed in tissues with high cell division activity, and is expressed throughout the entire process of embryo formation. The AtCDC5 loss-of-function mutant is embryonic lethal. In order to investigate the function of AtCDC5 in vivo, we generated AtCDC5-RNAi plants in which the expression of AtCDC5 was reduced by RNA interference. We found that the G2 to M （G2/M） phase transition was affected in the AtCDC5-RNAi plants, and that endoreduplication was increased. Additionally, the maintenance of shoot apical meristem （SAM） function was disturbed in the AtCDC5-RNAi plants, in which both the WUSCHEL （WUS）- CLAVATA （CLV） and the SHOOT MERISTEMLESS （STM） pathways were impaired. In situ hybridization analysis showed that the expression of STMwas greatly reduced in the shoot apical cells of the AtCDC5-RNAi plants. Moreover, cyclinB1 or Histone4 was found to be expressed in some of these cells when the transcript of STM was undetectable. These results suggest that AtCDC5 is essential for the G2/M phase transition and may regulate the function of SAM by controlling the expression ofSTMand WUS.
基金supported by Foundation and Frontier Issues of Science and Technology Department of Henan Province (NO.122300410066)
文摘Objective:To identify the influence on radiosensitivity of lung glandular cancer cells when excisions repair cross-complementing group1(ERCC1) gene was silenced by targeted siR NA.Methods:siR NA which targeting to ERCC1 and control siR NA was designed and synthesized.The human lung glandular cancer SPC-A-1 cells was transfected.A total of 56 nude mice were divided into two groups,and two kinds of SPC-A-1 cells were transplanted to armpit of right forelimb,to establish the nude mice subcutaneous xenotransplanted tumor model of human lung glandular cancer cells.After the tumor was developed,the nude mice were randomly divided into four groups and accepted different doses of X-Ray radiation,then the change of tumor volume,survival time of mice in every group were recorded and the average lifetime was calculated.Twenty-one days later of X-ray experiment,two mice were taken and sacrificed in each group and the tumors organizations were stripped.The cell apoptosis rate and cell cycle distributions were obtained by FCM(flow cytometry).Results:The volume of tumor which ERCC1 gene was silenced was less than single irradiation group after X-ray irradiation,and the growth speed was slower and the lifetime of mice was lengthened as well(P<0.05).The cells apoptosis rate and the rate of G2/M cells which ERCC1 gene was silenced were higher than the same dose control group and the rate of G_1 cells were lower,which indicated that the cells could be stopped at G_2/M point,the cell proliferation was inhibited,the cell apoptosis was promoted and the radiation sensitivity was improved after the ERCC1 was silenced.Conclusions:The radiation sensitivity of lung glandular tumor could be improved after the ERCC1 gene was silenced by siR NA.
