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
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-...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 of PCNA 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
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 of PCNA 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.
