RESUMO
Objective To explore whether alcohol promotes the development of breast cancer in TA2 mice and the possible potential mechanism. Methods Thirty-two 6-8-week old nulliparous female TA2 mice were randomly divided into control and ethanol-exposure groups, 16 mice in each group. The mice of the ethanol-exposure group were given 2%ethanol in drinking water, and the mice of control group received regular drinking water. Serum ethanol concentration in the TA2 mice was measured using an ANALOX AM1 alcohol analyzer. The incidence of breast cancer, tumor growth rate and tumor size of the ethanol-exposure and control groups were observed and compared. The estrogen levels of the two groups was detected by enzyme-linked immunosorbent assay ( ELASA) . Results Compared with the control group, the tumor for-mation rate of spontaneous breast cancer in the alcohol-exposure group was significantly increased (62. 5% vs. 43. 75%, P<0. 05), the average number of days of tumor formation was shortened (285 days vs. 335 days, P<0. 05), the tumor weight and volume were increased but not significant ( P>0. 05 ) , and the level of estrogen in the ethanol-exposure mice was significantly higher than that in the control group ( P>0. 05 ) . Conclusions Alcohol promotes the tumorigenesis of spontaneous breast cancer in TA2 mice, which may be associated to the increase of estrogen levels.
RESUMO
AIM:To investigate the effects of chronic hypoxia on the aggressiveness of MCF-7, a human breast cancer cell line , and the underlying mechanisms .METHODS: MCF-7 cells were cultured under hypoxia ( 1% O2 , 5%CO2 and 94%N2 ) or control (95%O2 and 5%CO2 ) condition.The viability, proliferation, and invasion and migration abilities of the MCF-7 cells were determined by MTT assay , CCK-8 assay, cell counting, and cell invasion and migration assays.Anchorage-independent growth and the alteration of cellular polarization of the MCF-7 cells were tested by soft agar colony formation assay and Matrigel-3D culture assay, respectively.The effects of chronic hypoxia on the growth and metas-tasis of MCF-7 cells in vivo were investigated by xenograft in nude mice .The morphological changes of the MCF-7 cells were observed under an inverted microscope .Hypoxia-induced alterations in the levels of hypoxia inducible factor-1 ( HIF-1 ) and phosphorylated glycogen synthase kinase-3β( p-GSK-3β) as well as epithelial-mesenchymal transition ( EMT) mol-ecules, such as E-cadherin, N-cadherin, vimentin, matrix metalloproteinase ( MMP)-3 and MMP-9, were determined by Western blot .RESULTS:Chronic hypoxia significantly increased the viability , proliferation , and invasion and migration abilities of MCF-7 cells in vitro, enhanced the anchorage-independent growth , facilitated cellular polarization alteration in Matrigel-3D culture, and promoted cancer metastasis in vivo.Hypoxia up-regulated HIF-1, activated GSK-3β, down-regu-lated E-cadherin and increased the protein levels of N-cadherin, vimentin, MMP-3 and MMP-9.CONCLUSION:Chronic hypoxia enhances the aggressiveness of breast cancer cells probably through EMT .
RESUMO
Objective To explore whether alcohol promotes the development of breast cancer in TA2 mice and the possible potential mechanism. Methods Thirty-two 6-8-week old nulliparous female TA2 mice were randomly divided into control and ethanol-exposure groups, 16 mice in each group. The mice of the ethanol-exposure group were given 2%ethanol in drinking water, and the mice of control group received regular drinking water. Serum ethanol concentration in the TA2 mice was measured using an ANALOX AM1 alcohol analyzer. The incidence of breast cancer, tumor growth rate and tumor size of the ethanol-exposure and control groups were observed and compared. The estrogen levels of the two groups was detected by enzyme-linked immunosorbent assay ( ELASA) . Results Compared with the control group, the tumor for-mation rate of spontaneous breast cancer in the alcohol-exposure group was significantly increased (62. 5% vs. 43. 75%, P<0. 05), the average number of days of tumor formation was shortened (285 days vs. 335 days, P<0. 05), the tumor weight and volume were increased but not significant ( P>0. 05 ) , and the level of estrogen in the ethanol-exposure mice was significantly higher than that in the control group ( P>0. 05 ) . Conclusions Alcohol promotes the tumorigenesis of spontaneous breast cancer in TA2 mice, which may be associated to the increase of estrogen levels.
RESUMO
AIM:To investigate the effects of chronic hypoxia on the aggressiveness of MCF-7, a human breast cancer cell line , and the underlying mechanisms .METHODS: MCF-7 cells were cultured under hypoxia ( 1% O2 , 5%CO2 and 94%N2 ) or control (95%O2 and 5%CO2 ) condition.The viability, proliferation, and invasion and migration abilities of the MCF-7 cells were determined by MTT assay , CCK-8 assay, cell counting, and cell invasion and migration assays.Anchorage-independent growth and the alteration of cellular polarization of the MCF-7 cells were tested by soft agar colony formation assay and Matrigel-3D culture assay, respectively.The effects of chronic hypoxia on the growth and metas-tasis of MCF-7 cells in vivo were investigated by xenograft in nude mice .The morphological changes of the MCF-7 cells were observed under an inverted microscope .Hypoxia-induced alterations in the levels of hypoxia inducible factor-1 ( HIF-1 ) and phosphorylated glycogen synthase kinase-3β( p-GSK-3β) as well as epithelial-mesenchymal transition ( EMT) mol-ecules, such as E-cadherin, N-cadherin, vimentin, matrix metalloproteinase ( MMP)-3 and MMP-9, were determined by Western blot .RESULTS:Chronic hypoxia significantly increased the viability , proliferation , and invasion and migration abilities of MCF-7 cells in vitro, enhanced the anchorage-independent growth , facilitated cellular polarization alteration in Matrigel-3D culture, and promoted cancer metastasis in vivo.Hypoxia up-regulated HIF-1, activated GSK-3β, down-regu-lated E-cadherin and increased the protein levels of N-cadherin, vimentin, MMP-3 and MMP-9.CONCLUSION:Chronic hypoxia enhances the aggressiveness of breast cancer cells probably through EMT .
RESUMO
Objective Epidemiological studies have suggested that alcohol drinking is closely associated with di-verse tumor development, but fewer laboratory studies or mechanism analysis is made. Our study aims to explore the effect of alcohol on the tumorigenicity and metastasis of breast cancer in nude mice in vivo and on the malignant behavior in vitro, and whether it is related to endoplasmic reticulum stress ( ERS) . Methods We first established the nude mouse model of breast cancer with chronic alcohol consumption (2%) and to detect the effects of ethanol on tumor growth and metastasis. We also observed the changes of malignant biological behavior of EO771 cells in cell culture induced by chronic alcohol treatment (0. 2%) using MTT, Transwell and soft agar tests, and detect the expression of ROS and ERS marker, i. e. p?eIF2a, Bip, and XBP1?s. Results The in vivo experiment showed that alcohol drinking enhanced the growth and metasta?ses of breast cancer in nude mice. The in vitro test showed that chronic exposure to ethanol also promoted the cell prolifera?tion and migration ability, increased the ROS expression, activated ERS pathway, and enhanced the expression of p?eIF2a, Bip and XBP1?s. Conclusions Alcohol drinking may promote the malignant behavior of breast cancer cells through endo?plasmic reticulum stress.