Objective: To study the reversal effect of neferine on adriamycin (ADM) resistant human breast cancer cell line MCF-7/ADM. Methods: The cytotoxic effect of Nef or ADM was determined by 3-[4, 5-dimethylthiazol-2.-yl], ...Objective: To study the reversal effect of neferine on adriamycin (ADM) resistant human breast cancer cell line MCF-7/ADM. Methods: The cytotoxic effect of Nef or ADM was determined by 3-[4, 5-dimethylthiazol-2.-yl], 5-diphenyl tetraxolium bromid (MTT) assay. Apoptosis and the expression of P-glycoprotein (P-gp) were detected by flow cytometry (FCM). The intracellular ADM concentration was measured by HPLC. Results: Nef at 1, 5, 10 mol/L decreased the IC50 of ADM to MCF-7/ADM from 11.63 g/mL to 4.59, 2.44, 0.27 g/mL respectively. MCF-7/ADM could resist the apoptosis induced by ADM while Nef (1-10 mol/L) could augment ADR-mediated apoptosis. Nef (10 mol/L) increased the accumulation of ADM up to 2.88 fold in MCF-7/ADM but not in sensitive cells MCF-7/S and reduced the expression of P-gp in MCF-7/ADM cells. Conclusion: Nef can circumvent multidrug resistance (MDR) of MCF-7/ADM cells and the mechanism was associated with the increase of intracellular accumulation of ADM and the reduced expression of P-gp in MCF-7/ADM cells.展开更多
Multidrug resistance（MDR） plays a major obstacle to successful gastric cancer chemotherapy.The purpose of this study was to investigate the MDR reversal effect and mechanisms of hyperthermia in combination with nefe...Multidrug resistance（MDR） plays a major obstacle to successful gastric cancer chemotherapy.The purpose of this study was to investigate the MDR reversal effect and mechanisms of hyperthermia in combination with neferine（Nef） in adriamycin（ADM） resistant human SGC7901/ADM gastric cancer cells.The MDR cells were heated at 42℃ and 45℃ for 30 min alone or combined with 10 μg/mL Nef.The cytotoxic effect of ADM was evaluated by MTT assay.Cellular plasma membrane lipid fluidity was detected by fluorescence polarization technique.Intracellular accumulation of ADM was monitored with high performance liquid chromatography.Mdr-1 mRNA,P-glycoprotein（P-gp）,γH2AX expression and γH2AX foci formation were determined by real-time PCR,Western blot and immunocytochemical staining respectively.It was found that different heating methods induced different cytotoxic effects.Water submerged hyperthermia had the strongest cytotoxicity of ADM and Nef combined with hyperthermia had a synergistic cytotoxicity of ADM in the MDR cells.The water submerged hyperthermia increased the cell membrane fluidity.Both water submerged hyperthermia and Nef increased the intracellular accumulation of ADM.The water submerged hyperthermia and Nef down-regulated the expression of mdr-1 mRNA and P-gp.The water submerged hyperthermia could damage DNA and increase the γH2AX expression of SGC7901/ADM cells.The higher temperature was,the worse effect was.Our results show that combined treatment of hyperthermia with Nef can synergistically reverse MDR in human SGC7901/ADM gastric cancer cells.展开更多
AIM： To observe the therapeutic effects of liposomeencapsulated adriamycin （LADM） on hepatoma in comparison with adriamycin solution （FADM） and adriarnycin plus blank liposome （ADM ＋ BL） administered into the ...AIM： To observe the therapeutic effects of liposomeencapsulated adriamycin （LADM） on hepatoma in comparison with adriamycin solution （FADM） and adriarnycin plus blank liposome （ADM ＋ BL） administered into the hepatic artery of rats. METHODS： LADM was prepared by pH gradient-driven method. Normal saline, FADM （2 mg/kg）, ADM＋BL （2 mg/kg）, and LADM （2 mg/kg） were injected via the hepatic artery in rats bearing liver W256 carcinosarcoma, which were divided into four groups randomly. The therapeutic effects were evaluated in terms of survival time, tumor enlargement ratio, and tumor necrosis degree. The difference was determined with ANOVA and Dunnett test and log rank test. RESULTS： Compared to FADM or ADM ＋ BL, LADM produced a more significant tumor inhibition （tumor volume ratio： 1.243±0.523 vs 1.883±0.708, 1.847±0.661, P 〈 0.01）, and more extensive tumor necrosis. The increased life span was prolonged significantly in rats receiving LADM compared with FADM or ADM＋BL （231.48 vs 74.66, 94.70） （P 〈 0.05）. CONCLUSION： The anticancer efficacies of adriamycin on hepatoma can be strongly improved by liposomal encapsulation through hepatic arterial administration.展开更多
Objective： To assess the inhibitory effects of liposomal adriamycin （LADR） locally injected into mammary glands of VX2 tumor-bearing rabbits on proliferation of lymph nodal metastatic cells. Methods： Twenty-one VX...Objective： To assess the inhibitory effects of liposomal adriamycin （LADR） locally injected into mammary glands of VX2 tumor-bearing rabbits on proliferation of lymph nodal metastatic cells. Methods： Twenty-one VX2 tumor-bearing rabbits were randomly and equally divided into 3 groups. Rabbits were randomized to receive sham treatment （Group I）, subcutaneous LADR around tumor （Group Ⅱ） and intravenous free adriamycin （Group Ⅲ）, respectively. Breast tumor and axillary lymph nodes were harvested after 3 repeated treatment. Nodal sizes of both pre-and post-treatment were measured. Proliferating cell nuclear antigen （PCNA） mRNA in both tumor and lymph nodes were determined by RT-PCR. Results： The mean size of axillary lymph nodes in Group I, Ⅱ and Ⅲ increased by 3.70%, 1.55% and 2.89%, respectively, with significant difference between Group Ⅲ and I （P=-0.004） and between Group Ⅱ and Ⅲ（P=-0.002）. Relative expression values of PCNA mRNA in breast tumors of Group I, Ⅱ and Ⅲ were 0.486, 0.513 and 0.396, respectively. For Group Ⅲ, PCNA mRNA was significantly less expressed than that in Group I （P=-0.023） and Ⅱ（P=0.005）. Relative expression values of PCNA mRNA in axillary lymph nodes of Group I, Ⅱ and Ⅲ were 0.541, 0.329 and 0.450, respectively. Compared with Group I, Group Ⅲ showed a markedly decreased expression of PCNA （P=-0.021）. The least level ofPCNA mRNA was found in Group Ⅱ, with a significant difference from that in Group Ⅲ（P=-0.004）. Conclusion： Local injection of LADR was an effective therapeutic regimen for lymphatic metastases from breast cancer, regardless of its little effect on primary tumor.展开更多
文摘Objective: To study the reversal effect of neferine on adriamycin (ADM) resistant human breast cancer cell line MCF-7/ADM. Methods: The cytotoxic effect of Nef or ADM was determined by 3-[4, 5-dimethylthiazol-2.-yl], 5-diphenyl tetraxolium bromid (MTT) assay. Apoptosis and the expression of P-glycoprotein (P-gp) were detected by flow cytometry (FCM). The intracellular ADM concentration was measured by HPLC. Results: Nef at 1, 5, 10 mol/L decreased the IC50 of ADM to MCF-7/ADM from 11.63 g/mL to 4.59, 2.44, 0.27 g/mL respectively. MCF-7/ADM could resist the apoptosis induced by ADM while Nef (1-10 mol/L) could augment ADR-mediated apoptosis. Nef (10 mol/L) increased the accumulation of ADM up to 2.88 fold in MCF-7/ADM but not in sensitive cells MCF-7/S and reduced the expression of P-gp in MCF-7/ADM cells. Conclusion: Nef can circumvent multidrug resistance (MDR) of MCF-7/ADM cells and the mechanism was associated with the increase of intracellular accumulation of ADM and the reduced expression of P-gp in MCF-7/ADM cells.
基金supported by grants from Natural Science Foundation of Hunan Province(No.07JJ4009)Project of the Department of Science and Technology of Hunan Province(No. 2010FJ6029)+2 种基金Research and Innovation Conditions Project of Hunan Province(No.2010TT2034)125 Talent Project of the Third Xiangya Hospital of Central South Universitythe Freedom Explore Program of Central South University(No. 2011QNZT193),China
文摘Multidrug resistance（MDR） plays a major obstacle to successful gastric cancer chemotherapy.The purpose of this study was to investigate the MDR reversal effect and mechanisms of hyperthermia in combination with neferine（Nef） in adriamycin（ADM） resistant human SGC7901/ADM gastric cancer cells.The MDR cells were heated at 42℃ and 45℃ for 30 min alone or combined with 10 μg/mL Nef.The cytotoxic effect of ADM was evaluated by MTT assay.Cellular plasma membrane lipid fluidity was detected by fluorescence polarization technique.Intracellular accumulation of ADM was monitored with high performance liquid chromatography.Mdr-1 mRNA,P-glycoprotein（P-gp）,γH2AX expression and γH2AX foci formation were determined by real-time PCR,Western blot and immunocytochemical staining respectively.It was found that different heating methods induced different cytotoxic effects.Water submerged hyperthermia had the strongest cytotoxicity of ADM and Nef combined with hyperthermia had a synergistic cytotoxicity of ADM in the MDR cells.The water submerged hyperthermia increased the cell membrane fluidity.Both water submerged hyperthermia and Nef increased the intracellular accumulation of ADM.The water submerged hyperthermia and Nef down-regulated the expression of mdr-1 mRNA and P-gp.The water submerged hyperthermia could damage DNA and increase the γH2AX expression of SGC7901/ADM cells.The higher temperature was,the worse effect was.Our results show that combined treatment of hyperthermia with Nef can synergistically reverse MDR in human SGC7901/ADM gastric cancer cells.
文摘AIM： To observe the therapeutic effects of liposomeencapsulated adriamycin （LADM） on hepatoma in comparison with adriamycin solution （FADM） and adriarnycin plus blank liposome （ADM ＋ BL） administered into the hepatic artery of rats. METHODS： LADM was prepared by pH gradient-driven method. Normal saline, FADM （2 mg/kg）, ADM＋BL （2 mg/kg）, and LADM （2 mg/kg） were injected via the hepatic artery in rats bearing liver W256 carcinosarcoma, which were divided into four groups randomly. The therapeutic effects were evaluated in terms of survival time, tumor enlargement ratio, and tumor necrosis degree. The difference was determined with ANOVA and Dunnett test and log rank test. RESULTS： Compared to FADM or ADM ＋ BL, LADM produced a more significant tumor inhibition （tumor volume ratio： 1.243±0.523 vs 1.883±0.708, 1.847±0.661, P 〈 0.01）, and more extensive tumor necrosis. The increased life span was prolonged significantly in rats receiving LADM compared with FADM or ADM＋BL （231.48 vs 74.66, 94.70） （P 〈 0.05）. CONCLUSION： The anticancer efficacies of adriamycin on hepatoma can be strongly improved by liposomal encapsulation through hepatic arterial administration.
文摘Objective： To assess the inhibitory effects of liposomal adriamycin （LADR） locally injected into mammary glands of VX2 tumor-bearing rabbits on proliferation of lymph nodal metastatic cells. Methods： Twenty-one VX2 tumor-bearing rabbits were randomly and equally divided into 3 groups. Rabbits were randomized to receive sham treatment （Group I）, subcutaneous LADR around tumor （Group Ⅱ） and intravenous free adriamycin （Group Ⅲ）, respectively. Breast tumor and axillary lymph nodes were harvested after 3 repeated treatment. Nodal sizes of both pre-and post-treatment were measured. Proliferating cell nuclear antigen （PCNA） mRNA in both tumor and lymph nodes were determined by RT-PCR. Results： The mean size of axillary lymph nodes in Group I, Ⅱ and Ⅲ increased by 3.70%, 1.55% and 2.89%, respectively, with significant difference between Group Ⅲ and I （P=-0.004） and between Group Ⅱ and Ⅲ（P=-0.002）. Relative expression values of PCNA mRNA in breast tumors of Group I, Ⅱ and Ⅲ were 0.486, 0.513 and 0.396, respectively. For Group Ⅲ, PCNA mRNA was significantly less expressed than that in Group I （P=-0.023） and Ⅱ（P=0.005）. Relative expression values of PCNA mRNA in axillary lymph nodes of Group I, Ⅱ and Ⅲ were 0.541, 0.329 and 0.450, respectively. Compared with Group I, Group Ⅲ showed a markedly decreased expression of PCNA （P=-0.021）. The least level ofPCNA mRNA was found in Group Ⅱ, with a significant difference from that in Group Ⅲ（P=-0.004）. Conclusion： Local injection of LADR was an effective therapeutic regimen for lymphatic metastases from breast cancer, regardless of its little effect on primary tumor.
