Overcoming MDR by Ultrasound-Induced Hyperthermia and P-Glycoprotein Modulation

Yang, Liu; Lillehei, Kevin O.; Cobb, Wesley N.; Christians, Uwe; Ng, Ka‐Yun

doi:10.1006/bbrc.2001.5938

Cited by 21 publications

(13 citation statements)

References 17 publications

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“…These data demonstrated that hyperthermia and Nef had a synergistic cytotoxic effect of ADM in the SGC7901/ADM cells. There were also similar studies reporting that the combined effect of ultrasound-induced hyperthermia (USHT) and PSC 833 on cytotoxicity of doxorubicin far exceeded that produced by USHT or PSC 833 alone in MV522/Q6 and KB-V-1 cell lines [31,32] . After being treated by water submerged hyperthermia at 42°C and 45°C for 30 min or combined with Nef, the increased intracellular ADM accumulation in SGC7901/ADM cells at 1 h and 3 h indicates that hyperthermia combined with Nef treatment, acting directly or indirectly, can either inhibit P-gp pump function of ADM efflux or accelerate the passive ADM permeation to the tumor cells.…”

Section: Discussionmentioning

confidence: 87%

Synergistic effect of hyperthermia and neferine on reverse multidrug resistance in adriamycin-resistant SGC7901/ADM gastric cancer cells

Huang

Cao

et al. 2011

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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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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Section: Discussionmentioning

confidence: 87%

Synergistic effect of hyperthermia and neferine on reverse multidrug resistance in adriamycin-resistant SGC7901/ADM gastric cancer cells

Huang

Cao

et al. 2011

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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“…may enhance cellular uptake and cytotoxicity of doxorubicin by an increase of membrane permeability to P-gp substrates (Liu et al 2001a). When US was combined with MDR modulators, the cytotoxicity of doxorubicin could be significantly enhanced in drug-resistant cancer cells (Liu et al 2001b;Rapoport 2004), suggesting that the cytotoxic effect of anticancer drugs on MDR tumor cells was significantly higher than that produced by either US exposure or the MDR modulator alone. In this study, flow cytometry showed that US exposure could significantly increase the intracellular uptake of Rh123 in both HepG2 and HepG2/ADM tumor cells.…”

Section: Discussion and Summarymentioning

confidence: 99%

“…Recently, ultrasound (US) has been shown to open the cell membrane temporarily, and allowing delivery of drugs, proteins and genes into viable cells (Mitragotri 2005;Newman and Bettinger 2007;Pitt et al 2004;ter Haar 2007). US has also been used as a localised approach, in combination with chemotherapeutic agents or MDR modulators, to explore the possibility of enhancing the cytotoxicity of anticancer drugs in MDR tumor cells, and preliminary results were very encouraging (Liu et al 2001a(Liu et al , 2001bRapoport 2004). Our previous study found that US exposure could significantly increase the uptake of rhodamine 123 (Rh123) and adriamycin (ADM) by MDR-resistant tumor cells (HepG2/ADM) and that MDR tumor cells became more sensitive to anticancer agents after US exposure (Shao et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Optimization of Ultrasound-Mediated In Vitro Reversal of Multidrug Resistance in Human Hepatocarcinoma Cell Line HepG2

Zhai

Shao

Zhao

et al. 2008

Ultrasound in Medicine & Biology

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“…Polymeric excipients [92] and transcriptional regulators [93] have also been studied. Although heat shock has been reported to induce MDR in some cancer cells [94, 95], an increase in cellular drug uptake and cytotoxicity by ultrasound-induced hyperthermia was reported [96, 97]. Unfortunately, delivery of these modulators to the target tumor is as challenging as the drug delivery obstacles we face.…”

Section: Transport Barriers Of Tme and Drug Resistancementioning

confidence: 99%

Recapitulation of complex transport and action of drugs at the tumor microenvironment using tumor-microenvironment-on-chip

Han

Park

et al. 2016

Cancer Letters

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Targeted delivery aims to selectively distribute drugs to targeted tumor tissue but not to healthy tissue. This can address many of clinical challenges by maximizing the efficacy but minimizing the toxicity of anti-cancer drugs. However, complex tumor microenvironment poses various barriers hindering the transport of drugs and drug delivery systems. New tumor models that allow for the systematic study of these complex environments are highly desired to provide reliable test beds to develop drug delivery systems for targeted delivery. Recently, research efforts have yielded new in vitro tumor models, the so called tumor-microenvironment-on-chip, that recapitulate certain characteristics of the tumor microenvironment. These new models show benefits over other conventional tumor models, and have the potential to accelerate drug discovery and enable precision medicines. However, further research is warranted to overcome their limitations and to properly interpret the data obtained from these models. In this article, key features of the in vivo tumor microenvironment that are relevant to drug transport processes for targeted delivery was discussed, and the current status and challenges for developing in vitro transport model systems was reviewed.

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Overcoming MDR by Ultrasound-Induced Hyperthermia and P-Glycoprotein Modulation

Cited by 21 publications

References 17 publications

Synergistic effect of hyperthermia and neferine on reverse multidrug resistance in adriamycin-resistant SGC7901/ADM gastric cancer cells

Synergistic effect of hyperthermia and neferine on reverse multidrug resistance in adriamycin-resistant SGC7901/ADM gastric cancer cells

Optimization of Ultrasound-Mediated In Vitro Reversal of Multidrug Resistance in Human Hepatocarcinoma Cell Line HepG2

Recapitulation of complex transport and action of drugs at the tumor microenvironment using tumor-microenvironment-on-chip

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