AIM:To explore the correlation of the inherent cellular ROSlevel with the susceptibility of the digestive tract tumor cellsto apoptosis inducted by As_2O_3.METHODS:Two gastric cercinoma cell lines,SGC7901 andMKN45,and...AIM:To explore the correlation of the inherent cellular ROSlevel with the susceptibility of the digestive tract tumor cellsto apoptosis inducted by As_2O_3.METHODS:Two gastric cercinoma cell lines,SGC7901 andMKN45,and two esophageal carcinoma cell lines,EC/CUHKI(alternatively named EC1.71)and EC1867 with lowconcentration(2μmol·L^(-1))of As_2O_3 were cultured respectly,which confirmed the difference in apoptosis susceptibilitybetween SGC7901 and MKN45,and between EC/CUHK1 andEC1867.The cells were incubated withdihydrogenrhodamine123(DHR123),used as a ROScapture,in absence of As_2O_3.The fluorescent intensity ofrhodamine123,which was the product of cellular oxidationof DHR123,was detected by flow cytometry,and ROS wasmeasured.RESULTS:Apoptosis induced by a low concentration ofAs203 was more readily to occur in SGC7901(22.4%±2.4%)and EC/CUHK1(27.0%±2.9%)than in MKN45(2.1%±0.5%)and EC1867(0.8%±0.5%).In other words,SGC7901was more sensitive than MKN45 to As_2O_3,meanwhile EC/CUHK1 was more sensitive than EC1867 to As_2O_3.The levelof inherent cellular ROS in SGC7901(650±37)was higherthan that in MKN45(507±22)(P<0.01),and the level ofinherent cellular ROS in EC/CUHK1(462±17)was higherthan that in EC1867(187±12)(P<0.01).CONCLUSIONS.The cellular sensitivity to apoptosis inducedby As_2O_3 is associated with the difference in cellular ROSlevel.The inherent ROS level might determinate theapoptotic sensitivity of tumor cells to As_2O_3.展开更多
AIM:To study the methods of preparing the magnetic nano-microspheres of Fe2O3 and As2O3/Fe2O3 complexes and their therapeutic effects with magnetic fluid hyperthermia(MFH). METHODS:Nanospheres were prepared by chemica...AIM:To study the methods of preparing the magnetic nano-microspheres of Fe2O3 and As2O3/Fe2O3 complexes and their therapeutic effects with magnetic fluid hyperthermia(MFH). METHODS:Nanospheres were prepared by chemical co-precipitation and their shape and diameter were observed.Hemolysis,micronucleus,cell viability,and LD50 along with other in vivo tests were performed to evaluate the Fe2O3 microsphere biocompatibility.The inhibition ratio of tumors after Fe2O3 and As2O3/Fe2O3 injections combined with induced hyperthermia in xenograft human hepatocarcinoma was calculated. RESULTS:Fe2O3 and As2O3/Fe2O3 particles were round with an average diameter of 20 nm and 100 nm as observed under transmission electron microscope.Upon exposure to an alternating magnetic field(AMF),the temperature of the suspension of magnetic particles increased to 41-51℃,depending on different particle concentrations,and remained stable thereafter.Nanosized Fe2O3 microspheres are a new kind of biomaterial without cytotoxic effects.The LD50 of both Fe2O3 and As2O3/Fe2O3 in mice was higher than 5 g/kg.One to four weeks after Fe2O3 and As2O3/Fe2O3 complex injections into healthy pig livers,no significant differences were found in serum AST,ALT,BUN and Cr levels among thepigs of all groups(P>0.05),and no obvious pathological alterations were observed.After exposure to alternating magnetic fields,the inhibition ratio of the tumors was significantly different from controls in the Fe2O3 and As2O3/Fe2O3 groups(68.74% and 82.79%,respectively; P<0.01).Tumors of mice in treatment groups showed obvious necrosis,while normal tissues adjoining the tumor and internal organs did not. CONCLUSION:Fe2O3 and As2O3/Fe2O3 complexes exerted radiofrequency-induced hyperthermia and drug toxicity on tumors without any liver or kidney damage. Therefore,nanospheres are ideal carriers for tumortargeted therapy.展开更多
基金the grants from National Natural Science Foundation of China,No.39730270Shanghai Science and Technology Development fund of Education Committee No.2000B101
文摘AIM:To explore the correlation of the inherent cellular ROSlevel with the susceptibility of the digestive tract tumor cellsto apoptosis inducted by As_2O_3.METHODS:Two gastric cercinoma cell lines,SGC7901 andMKN45,and two esophageal carcinoma cell lines,EC/CUHKI(alternatively named EC1.71)and EC1867 with lowconcentration(2μmol·L^(-1))of As_2O_3 were cultured respectly,which confirmed the difference in apoptosis susceptibilitybetween SGC7901 and MKN45,and between EC/CUHK1 andEC1867.The cells were incubated withdihydrogenrhodamine123(DHR123),used as a ROScapture,in absence of As_2O_3.The fluorescent intensity ofrhodamine123,which was the product of cellular oxidationof DHR123,was detected by flow cytometry,and ROS wasmeasured.RESULTS:Apoptosis induced by a low concentration ofAs203 was more readily to occur in SGC7901(22.4%±2.4%)and EC/CUHK1(27.0%±2.9%)than in MKN45(2.1%±0.5%)and EC1867(0.8%±0.5%).In other words,SGC7901was more sensitive than MKN45 to As_2O_3,meanwhile EC/CUHK1 was more sensitive than EC1867 to As_2O_3.The levelof inherent cellular ROS in SGC7901(650±37)was higherthan that in MKN45(507±22)(P<0.01),and the level ofinherent cellular ROS in EC/CUHK1(462±17)was higherthan that in EC1867(187±12)(P<0.01).CONCLUSIONS.The cellular sensitivity to apoptosis inducedby As_2O_3 is associated with the difference in cellular ROSlevel.The inherent ROS level might determinate theapoptotic sensitivity of tumor cells to As_2O_3.
基金Supported by The National Natural Science Foundation of China,30770584the State 863 Plan,2002AA302207,2007AA03Z356
文摘AIM:To study the methods of preparing the magnetic nano-microspheres of Fe2O3 and As2O3/Fe2O3 complexes and their therapeutic effects with magnetic fluid hyperthermia(MFH). METHODS:Nanospheres were prepared by chemical co-precipitation and their shape and diameter were observed.Hemolysis,micronucleus,cell viability,and LD50 along with other in vivo tests were performed to evaluate the Fe2O3 microsphere biocompatibility.The inhibition ratio of tumors after Fe2O3 and As2O3/Fe2O3 injections combined with induced hyperthermia in xenograft human hepatocarcinoma was calculated. RESULTS:Fe2O3 and As2O3/Fe2O3 particles were round with an average diameter of 20 nm and 100 nm as observed under transmission electron microscope.Upon exposure to an alternating magnetic field(AMF),the temperature of the suspension of magnetic particles increased to 41-51℃,depending on different particle concentrations,and remained stable thereafter.Nanosized Fe2O3 microspheres are a new kind of biomaterial without cytotoxic effects.The LD50 of both Fe2O3 and As2O3/Fe2O3 in mice was higher than 5 g/kg.One to four weeks after Fe2O3 and As2O3/Fe2O3 complex injections into healthy pig livers,no significant differences were found in serum AST,ALT,BUN and Cr levels among thepigs of all groups(P>0.05),and no obvious pathological alterations were observed.After exposure to alternating magnetic fields,the inhibition ratio of the tumors was significantly different from controls in the Fe2O3 and As2O3/Fe2O3 groups(68.74% and 82.79%,respectively; P<0.01).Tumors of mice in treatment groups showed obvious necrosis,while normal tissues adjoining the tumor and internal organs did not. CONCLUSION:Fe2O3 and As2O3/Fe2O3 complexes exerted radiofrequency-induced hyperthermia and drug toxicity on tumors without any liver or kidney damage. Therefore,nanospheres are ideal carriers for tumortargeted therapy.
