Objective： To investigate the change of the cell cycle, apoptosis and radiosensitivity effect by COCl2 induced hypoxia in esophageal cancer line Eca109 cells in vitro. Methods： The hypoxia culture model induced by 1...Objective： To investigate the change of the cell cycle, apoptosis and radiosensitivity effect by COCl2 induced hypoxia in esophageal cancer line Eca109 cells in vitro. Methods： The hypoxia culture model induced by 150 microM COCl2 was established. The cell cycle and apoptosis were measured with flow cytometry （FCM）. The radiosensitivity was analysized with clonogenic assay after irradiation alone or combined with hypoxia in Eca109 cells in vitro. Results： Eca109 cells were treated with 150 microM COCl2 for 24 h, cell cycle arrest in G0/G1 phase increase and decreasing arrest in S phase with longer of hypoxiac time （0-24 h）, the other rate of cell cycle and apoptosis did not change obviously. The G2/M phase block was arrested obviously in radiation alone comparing with the hypoxia plus irradiated group, apoptosis did not occur in Eca109 cell line following irradiation. The DO value and cell surviving fraction of Eca109 cell was 2.48 Gy, 2.44 Gy and 97.33%, 96.33% in hypoxia and control group, respectively; the Dq value of Eca109 cell was 2.89 Gy, 0.52 Gy, the cell surviving fraction after radiation with 4 Gy was 48.3%, 21.7% in hypoxia and control group, respectively. The hypoxia decreased the radiosensitivity in esophageal cancer Eca109 cells with clonogenic assay. Conclusion： Hypoxia induced by COCl2 influences radiosensitivity of Eca109 cell through regulating cellular proliferation rates.展开更多
Autophagy is the basic catabolic progress involved in cell degradation of unnecessary or dysfunctional cellular components.It has been proven that autophagy could be utilized for cell survival under stresses.Hypoxic-p...Autophagy is the basic catabolic progress involved in cell degradation of unnecessary or dysfunctional cellular components.It has been proven that autophagy could be utilized for cell survival under stresses.Hypoxic-preconditioning(HPC)could reduce apoptosis induced by ischemia and hypoxia/serum deprivation(H/SD)in bone marrow-derived mesenchymal stem cells(BMSCs).Previous studies have shown that both leptin signaling and autophagy activation were involved in the protection against apoptosis induced by various stress,including ischemia-reperfusion.However,it has never been fully understood how leptin was involved in the protective effects conferred by autophagy.In the present study,we demonstrated that HPC can induce autophagy in BMSCs by increased LC3-II/LC3-I ratio and autophagosome formation.Interestingly,similar effects were also observed when BMSCs were pretreated with rapamycin.The beneficial effects offered by HPC were absent when BMSCs were incubated with autophagy inhibitor,3-methyladenine(3-MA).In addition,down-regulated leptin expression by leptin-shRNA also attenuated HPC-induced autophagy in BMSCs,which in turn was associated with increased apoptosis after exposed to sustained H/SD.Furthermore,increased AMP-activated protein kinase phosphorylation and decreased mammalian target of rapamycin phosphorylation that were observed in HPC-treated BMSCs can also be attenuated by down-regulation of leptin expression.Our data suggests that leptin has impact on HPC-induced autophagy in BMSCs which confers protection against apoptosis under H/SD,possibly through modulating both AMPK and mTOR pathway.展开更多
Hypoxia-inducible factor-1(HIF-1)is a key heterodimeric transcription factor for the cellular adaptive response to hypoxia,a common feature of the microenvironment in solid tumors.The transcriptional activity,protein ...Hypoxia-inducible factor-1(HIF-1)is a key heterodimeric transcription factor for the cellular adaptive response to hypoxia,a common feature of the microenvironment in solid tumors.The transcriptional activity,protein stabilization,protein-protein interactions and cellular localization of HIF-1α,an oxygen-sensitive subunit of HIF-1,are mainly modulated by various post-translational modifications.Recently,we reported that polycomb chromobox 4(Cbx4)governs the transcriptional activity of HIF-1αby enhancing its sumoylation at K391 and K477,through which Cbx4 potentiates angiogenesis of hepatocellular carcinoma.This review summarizes the current knowledge of HIF-1α sumoylation and its roles in the pathogenesis of cancer.展开更多
基金the Tackle Key Problems in Science andTechnology of Hebei Province (No. 052761764)
文摘Objective： To investigate the change of the cell cycle, apoptosis and radiosensitivity effect by COCl2 induced hypoxia in esophageal cancer line Eca109 cells in vitro. Methods： The hypoxia culture model induced by 150 microM COCl2 was established. The cell cycle and apoptosis were measured with flow cytometry （FCM）. The radiosensitivity was analysized with clonogenic assay after irradiation alone or combined with hypoxia in Eca109 cells in vitro. Results： Eca109 cells were treated with 150 microM COCl2 for 24 h, cell cycle arrest in G0/G1 phase increase and decreasing arrest in S phase with longer of hypoxiac time （0-24 h）, the other rate of cell cycle and apoptosis did not change obviously. The G2/M phase block was arrested obviously in radiation alone comparing with the hypoxia plus irradiated group, apoptosis did not occur in Eca109 cell line following irradiation. The DO value and cell surviving fraction of Eca109 cell was 2.48 Gy, 2.44 Gy and 97.33%, 96.33% in hypoxia and control group, respectively; the Dq value of Eca109 cell was 2.89 Gy, 0.52 Gy, the cell surviving fraction after radiation with 4 Gy was 48.3%, 21.7% in hypoxia and control group, respectively. The hypoxia decreased the radiosensitivity in esophageal cancer Eca109 cells with clonogenic assay. Conclusion： Hypoxia induced by COCl2 influences radiosensitivity of Eca109 cell through regulating cellular proliferation rates.
文摘Autophagy is the basic catabolic progress involved in cell degradation of unnecessary or dysfunctional cellular components.It has been proven that autophagy could be utilized for cell survival under stresses.Hypoxic-preconditioning(HPC)could reduce apoptosis induced by ischemia and hypoxia/serum deprivation(H/SD)in bone marrow-derived mesenchymal stem cells(BMSCs).Previous studies have shown that both leptin signaling and autophagy activation were involved in the protection against apoptosis induced by various stress,including ischemia-reperfusion.However,it has never been fully understood how leptin was involved in the protective effects conferred by autophagy.In the present study,we demonstrated that HPC can induce autophagy in BMSCs by increased LC3-II/LC3-I ratio and autophagosome formation.Interestingly,similar effects were also observed when BMSCs were pretreated with rapamycin.The beneficial effects offered by HPC were absent when BMSCs were incubated with autophagy inhibitor,3-methyladenine(3-MA).In addition,down-regulated leptin expression by leptin-shRNA also attenuated HPC-induced autophagy in BMSCs,which in turn was associated with increased apoptosis after exposed to sustained H/SD.Furthermore,increased AMP-activated protein kinase phosphorylation and decreased mammalian target of rapamycin phosphorylation that were observed in HPC-treated BMSCs can also be attenuated by down-regulation of leptin expression.Our data suggests that leptin has impact on HPC-induced autophagy in BMSCs which confers protection against apoptosis under H/SD,possibly through modulating both AMPK and mTOR pathway.
基金supported by grants from the National Natural Science Foundation of China (91213304,31101044)the National Basic Research Program of China (NO2009CB918404)+1 种基金Shanghai Science & Technology Committee (11JC1406800)Shanghai Committee of Education and Doctoral Innovation Fund Projects from Shanghai Jiao Tong University School of Medicine
文摘Hypoxia-inducible factor-1(HIF-1)is a key heterodimeric transcription factor for the cellular adaptive response to hypoxia,a common feature of the microenvironment in solid tumors.The transcriptional activity,protein stabilization,protein-protein interactions and cellular localization of HIF-1α,an oxygen-sensitive subunit of HIF-1,are mainly modulated by various post-translational modifications.Recently,we reported that polycomb chromobox 4(Cbx4)governs the transcriptional activity of HIF-1αby enhancing its sumoylation at K391 and K477,through which Cbx4 potentiates angiogenesis of hepatocellular carcinoma.This review summarizes the current knowledge of HIF-1α sumoylation and its roles in the pathogenesis of cancer.
