Synergistic effect of hyperthermia and neferine on reverse multidrug resistance in adriamycin-resistant SGC7901/ADM gastric cancer cells |
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Authors: | Chenghui Huang Yaping Li Peiguo Cao Zhaoxia Xie Zhiqiang Qin |
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Institution: | 1. Department of Oncology, Third Xiangya Hospital, Central South University, Changsha 410013, China 2. Epigenetics Research Center, Second Xiangya Hospital, Central South University, Changsha 410011, China 3. Department of Hematology, Xiangya Hospital, Central South University, Changsha 410078, China 4. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, USA |
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Abstract: | 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°C and 45°C 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. |
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Keywords: | gastric cancer multidrug resistance hyperthermia Neferine mdr-l P-glycoprotein adriamycin |
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