OBJECTIVE: To evaluate the effects of tetrandrine plus arsenic trioxide on HCC1937 cells, a triple negative breast cancer cell line, and to explore possible mechanisms.METHODS: The 3-(4,5-Dimethylthiazol-2-yl)-2, 5-di...OBJECTIVE: To evaluate the effects of tetrandrine plus arsenic trioxide on HCC1937 cells, a triple negative breast cancer cell line, and to explore possible mechanisms.METHODS: The 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide method was used to compare the antiproliferative effects of tetrandrine,arsenic trioxide alone and tetrandrine plus arsenic trioxide on HCC1937 cells. The median-effect principle(Chou-Talalay combination index method) was used to examine the interaction between the two drugs. Flow cytometry was used to evaluate effects of treatment with tetrandrine, arsenic trioxide or the combination of both on HCC1937 cell apoptosis. Real-time polymerase chain reaction and western blotting were performed to evaluate changes in apoptosis-related gene expression and protein levels.RESULTS: Tetrandrine and arsenic trioxide each in-hibited HCC1937 cell proliferation in a dose-dependent manner. The cell inhibition rate of HCC1937 cells treated with a combination of tetrandrine and arsenic trioxide was significantly higher than with either compound alone. The two drugs produced a synergistic effect when the inhibition rate was20%-40%. Flow cytometry results showed that treatment with the two drugs increased the proportion of apoptotic cells. In the combination treated group, caspase-3 activation and PARP cleavage were significantly higher than in the other groups.Moreover, Bcl-2 and survivin expression were decreased, whereas that of both Bid and Bax was increased.CONCLUSION: These findings demonstrated that tetrandrine plus arsenic trioxide had synergistic efficacy on induction of apoptosis in HCC1937 cells.展开更多
目的探讨薯蓣皂苷元对人三阴乳腺癌细胞系HCC1937增殖及凋亡的影响。方法对数生长期人三阴乳腺癌HCC1937细胞株分为空白组(培养液)、实验1组(培养液+10mg/L薯蓣皂苷元)、实验2组(培养液+25mg/L薯蓣皂苷元)。采用MTT法观察薯蓣皂苷元培...目的探讨薯蓣皂苷元对人三阴乳腺癌细胞系HCC1937增殖及凋亡的影响。方法对数生长期人三阴乳腺癌HCC1937细胞株分为空白组(培养液)、实验1组(培养液+10mg/L薯蓣皂苷元)、实验2组(培养液+25mg/L薯蓣皂苷元)。采用MTT法观察薯蓣皂苷元培养24、48、72h时HCC1937细胞生长抑制率;流式细胞仪检测薯蓣皂苷元培养48h时HCC1937细胞周期及细胞凋亡;Western blot法检测薯蓣皂苷元培养48h时Bcl-2、Bcl-2相关X蛋白(Bcl-2associated X protein,Bax)、P53、caspase3蛋白表达;Transwell实验观察薯蓣皂苷元培养24h时HCC1937细胞侵袭能力。结果薯蓣皂苷元培养24、48、72h,HCC1937细胞生长抑制率在实验1组分别为(6.86±2.56)%、(15.57±1.86)%、(14.84±4.64)%,在实验2组分别为(11.78±2.16)%、(24.48±3.70)%、(31.38±3.76)%,均高于空白组[(3.34±2.56)%、(8.47±1.86)%、(7.73±4.64)%](P<0.05),且实验2组高于实验1组(P<0.05);薯蓣皂苷元培养48h,实验1组G_1期细胞比例、细胞凋亡率分别为(36.21±3.12)%、(21.99±2.36)%,实验2组分别为(50.26±2.36)%、(26.17±3.46)%,均高于空白组[(28.35±2.54)%、(17.25±1.23)%](P<0.05),实验2组高于实验1组(P<0.05);薯蓣皂苷元培养24h,实验1组、实验2组HCC1937侵袭细胞数目[(64.00±11.01)%、(30.33±6.11)%]低于空白组[(146.00±9.16)%](P<0.05),实验2组低于实验1组(P<0.05);薯蓣皂苷元培养48h时,实验1组、实验2组HCC1937细胞Bcl-2表达量低于空白组,Bax、caspase3表达量高于空白组(P<0.05),实验1组Bcl-2表达量低于实验2组,Bax、caspase3表达量高于实验2组(P<0.05),3组P53蛋白表达量比较差异无统计学意义(P>0.05)。结论薯蓣皂苷元可抑制人三阴乳腺癌细胞系HCC1937增殖与侵袭,可能机制为使肿瘤细胞G_1期阻滞,下调抗凋亡蛋白Bcl-2表达,上调促凋亡蛋白Bax、caspase3表达。展开更多
The Triple Negative “Basal-like” breast cancer (TNBL) tumours have a high proliferative capacity and develop a resistance phenotype associated with metastases. However, the management of TNBL carcinomas is still not...The Triple Negative “Basal-like” breast cancer (TNBL) tumours have a high proliferative capacity and develop a resistance phenotype associated with metastases. However, the management of TNBL carcinomas is still not standardized. Among the promising trails, gold nanoparticles could be a relevant tool for the development of a targeted treatment for this breast cancer subtype in monotherapy, associated and/or conjugated with other drugs. In this work, we report the cytotoxicity impact of gold nanoparticles wrapped in Poly-Ethylene Glycol (PEG) on the TNBL HCC-1937 breast cancer cell line. PEG-coated gold nanoparticles (PEG-Au NPs) were synthesized by a two-step method using a reduction process followed by a post-functionalization called PEGylation. PEG-Au NPs were characterized using transmission electron microscopy and X-ray diffraction. The gold content of the samples was determined using atomic absorption spectrometer. The cytotoxicity tests were performed using Sulforhodamine B survival test and resazurin viability test. PEG-Au NPs impact analysis on HCC1937 TNBL cell line showed a clear toxic action of type dose dependent and at long term. These PEGylated gold nanoparticles present a promising tool for the development of tumor-specific radiosensitizing vectors, with or without the association of other treatment strategies.展开更多
基金Supported by the National Natural Science Foundation of China(Experimental Study on Tumor Microenvironment and Intervention of Lung Metastatic Breast Cancer with the Synergistic Effect of Arsenic Trioxide,No.81256203)
文摘OBJECTIVE: To evaluate the effects of tetrandrine plus arsenic trioxide on HCC1937 cells, a triple negative breast cancer cell line, and to explore possible mechanisms.METHODS: The 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide method was used to compare the antiproliferative effects of tetrandrine,arsenic trioxide alone and tetrandrine plus arsenic trioxide on HCC1937 cells. The median-effect principle(Chou-Talalay combination index method) was used to examine the interaction between the two drugs. Flow cytometry was used to evaluate effects of treatment with tetrandrine, arsenic trioxide or the combination of both on HCC1937 cell apoptosis. Real-time polymerase chain reaction and western blotting were performed to evaluate changes in apoptosis-related gene expression and protein levels.RESULTS: Tetrandrine and arsenic trioxide each in-hibited HCC1937 cell proliferation in a dose-dependent manner. The cell inhibition rate of HCC1937 cells treated with a combination of tetrandrine and arsenic trioxide was significantly higher than with either compound alone. The two drugs produced a synergistic effect when the inhibition rate was20%-40%. Flow cytometry results showed that treatment with the two drugs increased the proportion of apoptotic cells. In the combination treated group, caspase-3 activation and PARP cleavage were significantly higher than in the other groups.Moreover, Bcl-2 and survivin expression were decreased, whereas that of both Bid and Bax was increased.CONCLUSION: These findings demonstrated that tetrandrine plus arsenic trioxide had synergistic efficacy on induction of apoptosis in HCC1937 cells.
文摘目的探讨薯蓣皂苷元对人三阴乳腺癌细胞系HCC1937增殖及凋亡的影响。方法对数生长期人三阴乳腺癌HCC1937细胞株分为空白组(培养液)、实验1组(培养液+10mg/L薯蓣皂苷元)、实验2组(培养液+25mg/L薯蓣皂苷元)。采用MTT法观察薯蓣皂苷元培养24、48、72h时HCC1937细胞生长抑制率;流式细胞仪检测薯蓣皂苷元培养48h时HCC1937细胞周期及细胞凋亡;Western blot法检测薯蓣皂苷元培养48h时Bcl-2、Bcl-2相关X蛋白(Bcl-2associated X protein,Bax)、P53、caspase3蛋白表达;Transwell实验观察薯蓣皂苷元培养24h时HCC1937细胞侵袭能力。结果薯蓣皂苷元培养24、48、72h,HCC1937细胞生长抑制率在实验1组分别为(6.86±2.56)%、(15.57±1.86)%、(14.84±4.64)%,在实验2组分别为(11.78±2.16)%、(24.48±3.70)%、(31.38±3.76)%,均高于空白组[(3.34±2.56)%、(8.47±1.86)%、(7.73±4.64)%](P<0.05),且实验2组高于实验1组(P<0.05);薯蓣皂苷元培养48h,实验1组G_1期细胞比例、细胞凋亡率分别为(36.21±3.12)%、(21.99±2.36)%,实验2组分别为(50.26±2.36)%、(26.17±3.46)%,均高于空白组[(28.35±2.54)%、(17.25±1.23)%](P<0.05),实验2组高于实验1组(P<0.05);薯蓣皂苷元培养24h,实验1组、实验2组HCC1937侵袭细胞数目[(64.00±11.01)%、(30.33±6.11)%]低于空白组[(146.00±9.16)%](P<0.05),实验2组低于实验1组(P<0.05);薯蓣皂苷元培养48h时,实验1组、实验2组HCC1937细胞Bcl-2表达量低于空白组,Bax、caspase3表达量高于空白组(P<0.05),实验1组Bcl-2表达量低于实验2组,Bax、caspase3表达量高于实验2组(P<0.05),3组P53蛋白表达量比较差异无统计学意义(P>0.05)。结论薯蓣皂苷元可抑制人三阴乳腺癌细胞系HCC1937增殖与侵袭,可能机制为使肿瘤细胞G_1期阻滞,下调抗凋亡蛋白Bcl-2表达,上调促凋亡蛋白Bax、caspase3表达。
文摘The Triple Negative “Basal-like” breast cancer (TNBL) tumours have a high proliferative capacity and develop a resistance phenotype associated with metastases. However, the management of TNBL carcinomas is still not standardized. Among the promising trails, gold nanoparticles could be a relevant tool for the development of a targeted treatment for this breast cancer subtype in monotherapy, associated and/or conjugated with other drugs. In this work, we report the cytotoxicity impact of gold nanoparticles wrapped in Poly-Ethylene Glycol (PEG) on the TNBL HCC-1937 breast cancer cell line. PEG-coated gold nanoparticles (PEG-Au NPs) were synthesized by a two-step method using a reduction process followed by a post-functionalization called PEGylation. PEG-Au NPs were characterized using transmission electron microscopy and X-ray diffraction. The gold content of the samples was determined using atomic absorption spectrometer. The cytotoxicity tests were performed using Sulforhodamine B survival test and resazurin viability test. PEG-Au NPs impact analysis on HCC1937 TNBL cell line showed a clear toxic action of type dose dependent and at long term. These PEGylated gold nanoparticles present a promising tool for the development of tumor-specific radiosensitizing vectors, with or without the association of other treatment strategies.
