OBJECTIVE To determine the transcriptional expression of mitochondrial genome （mtDNA） in MGC803 cell lines subjected by various time-phase hypoxic dispositions, and further to discuss the influence of mtDNA transcri...OBJECTIVE To determine the transcriptional expression of mitochondrial genome （mtDNA） in MGC803 cell lines subjected by various time-phase hypoxic dispositions, and further to discuss the influence of mtDNA transcripts on hypoxic resistance to irradiation. METHODS The MGC803 cells exposed to anoxic environment were divided into control group （0 h）, hypoxic group （2 h, 8 h, 16 h, 24 h） and irradiated group after exposing the hypoxia. RTPCR was applied to detect the transcripts of cytochrome oxidase subunit Ⅰ （COI）, NADH dehydrogenase subunit 4 （ND4）, ND5, cytochrome b （cyt-b） and ATPase6 （ATP-6） in MGC803 cell lines at various time-phases of hypoxic, and after X-ray irradiation. Flow cytometry and colony formation assay were conducted to evaluate the cell cycle phase and survival fraction. RESULTS COI and ND4 transcripts of MGC803 cell lines were influenced remarkably by hypoxia. COI transcripts were decreased remarkably with the elongation time of exposing the hypoxic, and reduced to one fourth of its original amount of prehypoxia 24 h after exposing the hypoxia. ND4 transcripts were increased initially, and elevated to two folds 8 h after exposing the hypoxia, and then reduced to one second 24 h after exposing the hypoxia. Hypoxia resulted in G1 phase blockage, especially after hypoxia for 16 h. The survival fraction of MGCS03 ceils exposing the hypoxia in irradiated group showed that as the time of exposing the hypoxic before irradiation is prolonged, the survival fraction of MGC803 cells may have an elevated tendency. CONCLUSION The tumor cells with lower expression levels of the COI and the ND4 after exposing the hypoxic have stronger resistance to the radiation, which indicates that increasing the expression levels of the COI and the ND4 might be advantageous to enhance the sensitivity of hypoxic tumor cells to the radiotherapy.展开更多
Malabaricone C （1）, isolated from the seeds ofMyristicafragrans Houtt., belongs to a kind of diarylnonanoid compounds that are only found in Myristicaceae till now. In this study, biotransformation of 1 was investig...Malabaricone C （1）, isolated from the seeds ofMyristicafragrans Houtt., belongs to a kind of diarylnonanoid compounds that are only found in Myristicaceae till now. In this study, biotransformation of 1 was investigated using rat hepatic microsomes for the first time and the main biotransformation product was elucidated as malabaricone B （2） according to the spectroscopic data. Further evaluation on human gastric cancer cell lines showed that the cytotoxic effects of malabaricone C and its metabolite malabaricone B were comparable to those of vinorelbine, with the values of IC50 of （42.62±3.10） and （19.80±1.70） μg/mL on NCI-N87, and （22.94±1.33） and （19.60±2.21） μg/mL on MGC803, respectively. Statistical analysis revealed that malabaricone B had significantly stronger cytotoxicity than the parent compound （P〈0.01 on NCI-N87 and P〈0.05 on MGC803）, which may indicate a bioactivation of malabaricone C by hepatic microsomes. These results suggest that malabaricone C has a simple biotransformation pathway by hepatic microsomes and provide valuable information for further investigation on both the parent compound and its biotransformation product as anti-gastric cancer agents or lead compounds.展开更多
基金supported by a grant from the National Natural Science Foundation of China(No.30700979).
文摘OBJECTIVE To determine the transcriptional expression of mitochondrial genome （mtDNA） in MGC803 cell lines subjected by various time-phase hypoxic dispositions, and further to discuss the influence of mtDNA transcripts on hypoxic resistance to irradiation. METHODS The MGC803 cells exposed to anoxic environment were divided into control group （0 h）, hypoxic group （2 h, 8 h, 16 h, 24 h） and irradiated group after exposing the hypoxia. RTPCR was applied to detect the transcripts of cytochrome oxidase subunit Ⅰ （COI）, NADH dehydrogenase subunit 4 （ND4）, ND5, cytochrome b （cyt-b） and ATPase6 （ATP-6） in MGC803 cell lines at various time-phases of hypoxic, and after X-ray irradiation. Flow cytometry and colony formation assay were conducted to evaluate the cell cycle phase and survival fraction. RESULTS COI and ND4 transcripts of MGC803 cell lines were influenced remarkably by hypoxia. COI transcripts were decreased remarkably with the elongation time of exposing the hypoxic, and reduced to one fourth of its original amount of prehypoxia 24 h after exposing the hypoxia. ND4 transcripts were increased initially, and elevated to two folds 8 h after exposing the hypoxia, and then reduced to one second 24 h after exposing the hypoxia. Hypoxia resulted in G1 phase blockage, especially after hypoxia for 16 h. The survival fraction of MGCS03 ceils exposing the hypoxia in irradiated group showed that as the time of exposing the hypoxic before irradiation is prolonged, the survival fraction of MGC803 cells may have an elevated tendency. CONCLUSION The tumor cells with lower expression levels of the COI and the ND4 after exposing the hypoxic have stronger resistance to the radiation, which indicates that increasing the expression levels of the COI and the ND4 might be advantageous to enhance the sensitivity of hypoxic tumor cells to the radiotherapy.
基金National Natural Science Foundation of China(Grant No.30973863.81161120429)National Key Technology R&D Program of China(Grant No.2011BAI07B08)
文摘Malabaricone C （1）, isolated from the seeds ofMyristicafragrans Houtt., belongs to a kind of diarylnonanoid compounds that are only found in Myristicaceae till now. In this study, biotransformation of 1 was investigated using rat hepatic microsomes for the first time and the main biotransformation product was elucidated as malabaricone B （2） according to the spectroscopic data. Further evaluation on human gastric cancer cell lines showed that the cytotoxic effects of malabaricone C and its metabolite malabaricone B were comparable to those of vinorelbine, with the values of IC50 of （42.62±3.10） and （19.80±1.70） μg/mL on NCI-N87, and （22.94±1.33） and （19.60±2.21） μg/mL on MGC803, respectively. Statistical analysis revealed that malabaricone B had significantly stronger cytotoxicity than the parent compound （P〈0.01 on NCI-N87 and P〈0.05 on MGC803）, which may indicate a bioactivation of malabaricone C by hepatic microsomes. These results suggest that malabaricone C has a simple biotransformation pathway by hepatic microsomes and provide valuable information for further investigation on both the parent compound and its biotransformation product as anti-gastric cancer agents or lead compounds.
