AIM To investigate the response to hyperthermia and chemotherapy, analyzing apoptosis, cytotoxicity, and cisplatin concentration in different digestive system cancer cells.METHODS AGS(gastric cancer cell line), Caco-2...AIM To investigate the response to hyperthermia and chemotherapy, analyzing apoptosis, cytotoxicity, and cisplatin concentration in different digestive system cancer cells.METHODS AGS(gastric cancer cell line), Caco-2(colon cancer cell line) and T3M4(pancreatic cancer cell line) were treated by cisplatin and different temperature setting(37 ℃ to 45 ℃) either in isolation, or in combination. Treatment lasted for one hour. 48 h after the treatment viability was evaluated by MTT, cell apoptosis by Annexin V-PE and 7 ADD flow cytometry. Intracellular cisplatin concentration was measured immediately after the treatment, using mass spectrometry. Isobologram analysis was performed to evaluate the mathematical combined effect of temperature and cisplatin.RESULTS AGS cells were the most sensitive to isolated application of hyperthermia. Hyperthermia, in addition to cisplatin treatment, did not provoke a synergistic effect at intervals from 37 ℃ to 41 ℃ in neither cancer cell line. However, a temperature of 43 ℃ enhanced cisplatin cytotoxicity for Caco-2 cells. Moreover, isobologram analysis revealed mathematical antagonistic effects of cisplatin and temperature combined treatment in AGS cells; variations between synergistic, additive, and antagonistic effects in Caco-2 cells; and additive and antagonistic effects in T3 M4 cells. Combined treatment enhanced initiation of cell apoptosis in AGS, Caco-2, and T3 M4 cells by 61%, 20%, and 19% respectively. The increase of intracellular cisplatin concentration was observed at 43 ℃ by 30%, 20%, and 18% in AGS, Caco-2, and T3 M4 cells, respectively.CONCLUSION In addition to cisplatin, hyperthermia up to 43 ℃ does not affect the viability of cancer cells in a synergistic manner.展开更多
Objective： The combination effect of Piperbetle （PB） and 5-fluorouracil （5-FU） in enhancing the cytotoxic potential of 5-FU in inhibiting the growth of colon cancer cells was investigated. Methods： HT29 and HCT1...Objective： The combination effect of Piperbetle （PB） and 5-fluorouracil （5-FU） in enhancing the cytotoxic potential of 5-FU in inhibiting the growth of colon cancer cells was investigated. Methods： HT29 and HCT116 cells were subjected to 5-FU or PB treatment. 5-FU and PB were then combined and their effects on both cell lines were observed after 24 h of treatment. PB-5-FU interaction was elucidated by isobologram analysis. Apoptosis features of the treated cells were revealed by annexin V/PI stain. High-performance liquid chromatography （HPLC） was performed to exclude any possible chemical interaction between the compounds. Results： In the presence of PB extract, the cytotoxicity of 5-FU was observed at a lower dose （IC^0 12.5 pmol/L） and a shorter time （24 h） in both cell lines. Both cell lines treated with 5-FU or PB alone induced a greater apoptosis effect compared with the combination treatment. Isobologram analysis indicated that PB and 5-FU interacted synergistically and antagonistically in inhibiting the growth of HT29 and HCT116 cells, respectively. Conclusions： In the presence of PB, a lower dosage of 5-FU is required to achieve the maximum drug effect in inhibiting the growth of HT29 cells. However, PB did not significantly reduce 5-FU dosage in HCT116 cells. Our result showed that this interaction may not solely contribute to the apoptosis pathway.展开更多
基金Supported by the Research Council of Lithuania,No.SEN-01/2015
文摘AIM To investigate the response to hyperthermia and chemotherapy, analyzing apoptosis, cytotoxicity, and cisplatin concentration in different digestive system cancer cells.METHODS AGS(gastric cancer cell line), Caco-2(colon cancer cell line) and T3M4(pancreatic cancer cell line) were treated by cisplatin and different temperature setting(37 ℃ to 45 ℃) either in isolation, or in combination. Treatment lasted for one hour. 48 h after the treatment viability was evaluated by MTT, cell apoptosis by Annexin V-PE and 7 ADD flow cytometry. Intracellular cisplatin concentration was measured immediately after the treatment, using mass spectrometry. Isobologram analysis was performed to evaluate the mathematical combined effect of temperature and cisplatin.RESULTS AGS cells were the most sensitive to isolated application of hyperthermia. Hyperthermia, in addition to cisplatin treatment, did not provoke a synergistic effect at intervals from 37 ℃ to 41 ℃ in neither cancer cell line. However, a temperature of 43 ℃ enhanced cisplatin cytotoxicity for Caco-2 cells. Moreover, isobologram analysis revealed mathematical antagonistic effects of cisplatin and temperature combined treatment in AGS cells; variations between synergistic, additive, and antagonistic effects in Caco-2 cells; and additive and antagonistic effects in T3 M4 cells. Combined treatment enhanced initiation of cell apoptosis in AGS, Caco-2, and T3 M4 cells by 61%, 20%, and 19% respectively. The increase of intracellular cisplatin concentration was observed at 43 ℃ by 30%, 20%, and 18% in AGS, Caco-2, and T3 M4 cells, respectively.CONCLUSION In addition to cisplatin, hyperthermia up to 43 ℃ does not affect the viability of cancer cells in a synergistic manner.
基金supported by the Ministry of Higher Education,Malaysia(No.UKM-JJ-03-FRGS0044-2010)Universiti Kebangsaan Malaysia(No.UKM-DPP-2014-131)
文摘Objective： The combination effect of Piperbetle （PB） and 5-fluorouracil （5-FU） in enhancing the cytotoxic potential of 5-FU in inhibiting the growth of colon cancer cells was investigated. Methods： HT29 and HCT116 cells were subjected to 5-FU or PB treatment. 5-FU and PB were then combined and their effects on both cell lines were observed after 24 h of treatment. PB-5-FU interaction was elucidated by isobologram analysis. Apoptosis features of the treated cells were revealed by annexin V/PI stain. High-performance liquid chromatography （HPLC） was performed to exclude any possible chemical interaction between the compounds. Results： In the presence of PB extract, the cytotoxicity of 5-FU was observed at a lower dose （IC^0 12.5 pmol/L） and a shorter time （24 h） in both cell lines. Both cell lines treated with 5-FU or PB alone induced a greater apoptosis effect compared with the combination treatment. Isobologram analysis indicated that PB and 5-FU interacted synergistically and antagonistically in inhibiting the growth of HT29 and HCT116 cells, respectively. Conclusions： In the presence of PB, a lower dosage of 5-FU is required to achieve the maximum drug effect in inhibiting the growth of HT29 cells. However, PB did not significantly reduce 5-FU dosage in HCT116 cells. Our result showed that this interaction may not solely contribute to the apoptosis pathway.
