The effects of ultrasound exposure on P-glycoprotein-mediated multidrug resistance in vitro and in vivo

Huang, Chixiong; Huang, Suming; Li, Hairui; Li, Xinzhong; Li, Bing; Zhong, Lintao; Wang, Junfeng; Zou, Meishen; He, Xiang; Zheng, Hao; Si, Xiaoyan; Liao, Wangjun; Liao, Yulin; Yang, Li; Bin, Jianping

doi:10.1186/s13046-018-0900-6

Cited by 18 publications

(12 citation statements)

References 55 publications

(53 reference statements)

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“…Focused US has been used recently to target DNA-loaded microbubbles located within tumor’s neovasculature to facilitate release of genetic material locally into the tumor [35, 36]. In particular, US has been noted causing the process of sonoporation thus producing transient pores in the cancer cell membranes through which molecules are able to enter the cell [20, 37, 38]. Of interest, successful delivery of genetic material by using microbubbles induces apoptosis in cancer cells and reduces tumor growth [39, 40].…”

Section: Discussionmentioning

confidence: 99%

Very low intensity ultrasounds as a new strategy to improve selective delivery of nanoparticles-complexes in cancer cells

Loria

Giliberti

Bedini

et al. 2019

J Exp Clin Cancer Res

336

233

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BackgroundThe possibility to combine Low Intensity UltraSound (LIUS) and Nanoparticles (NP) could represent a promising strategy for drugs delivery in tumors difficult to treat overcoming resistance to therapies. On one side the NP can carry drugs that specifically target the tumors on the other the LIUS can facilitate and direct the delivery to the tumor cells. In this study, we investigated whether Very Low Intensity UltraSound (VLIUS), at intensities lower than 120 mW/cm2, might constitute a novel strategy to improve delivery to tumor cells. Thus, in order to verify the efficacy of this novel modality in terms of increase selective uptake in tumoral cells and translate speedily in clinical practice, we investigated VLIUS in three different in vitro experimental tumor models and normal cells adopting three different therapeutic strategies.MethodsVLIUS at different intensities and exposure time were applied to tumor and normal cells to evaluate the efficiency in uptake of labeled human ferritin (HFt)-based NP, the delivery of NP complexed Firefly luciferase reported gene (lipoplex-LUC), and the tumor-killing of chemotherapeutic agent.ResultsSpecifically, we found that specific VLIUS intensity (120 mW/cm2) increases tumor cell uptake of HFt-based NPs at specific concentration (0.5 mg/ml). Similarly, VLIUS treatments increase significantly tumor cells delivery of lipoplex-LUC cargos. Furthermore, of interest, VLIUS increases tumor killing of chemotherapy drug trabectedin in a time dependent fashion. Noteworthy, VLIUS treatments are well tolerated in normal cells with not significant effects on cell survival, NPs delivery and drug-induced toxicity, suggesting a tumor specific fashion.ConclusionsOur data shed novel lights on the potential application of VLIUS for the design and development of novel therapeutic strategies aiming to efficiently deliver NP loaded cargos or anticancer drugs into more aggressive and unresponsive tumors niche.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-1018-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Very low intensity ultrasounds as a new strategy to improve selective delivery of nanoparticles-complexes in cancer cells

Loria

Giliberti

Bedini

et al. 2019

J Exp Clin Cancer Res

336

233

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“…Then, the cells were fixed with 4% polyoxymethylene, permeabilized with 0.2% Triton X-100 and blocked with PBS containing 5% bovine serum albumin. The immunofluorescence analysis was performed as described previously 30, 31. The primary antibody details are available in Table S6.…”

Section: Methodsmentioning

confidence: 99%

Long noncoding RNA GAS5 induces abdominal aortic aneurysm formation by promoting smooth muscle apoptosis

He¹,

Wang²,

Li³

et al. 2019

Theranostics

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Objective: Long noncoding RNAs (lncRNAs) may serve as specific targets for the treatment of abdominal aortic aneurysms (AAAs). LncRNA GAS5, functionally associated with smooth muscle cell (SMC) apoptosis and proliferation, is likely involved in AAA formation, but the exact role of GAS5 in AAA is unknown. We thus explored the contribution of GAS5 to SMC-regulated AAA formation and its underlying mechanisms.Methods: Human specimens were used to verify the diverse expression of GAS5 in normal and AAA tissues. The angiotensin II (Ang II)-induced AAA model in ApoE-/- mice and the CaCl2-induced AAA model in wild-type C57BL/6 mice were used. RNA pull-down and luciferase reporter gene assays were performed in human aortic SMCs to detect the interaction between GAS5 and its downstream targets of protein or microRNA (miR).Results: GAS5 expression was significantly upregulated in human AAA specimens and two murine AAA models compared to human normal aortas and murine sham-operated controls. GAS5 overexpression induced SMC apoptosis and repressed its proliferation, thereby promoting AAA formation in two murine AAA models. Y-box-binding protein 1 (YBX1) was identified as a direct target of GAS5 while it also formed a positive feedback loop with GAS5 to regulate the downstream target p21. Furthermore, GAS5 acted as a miR-21 sponge to release phosphatase and tensin homolog from repression, which blocked the activation and phosphorylation of Akt to inhibit proliferation and promote apoptosis in SMCs.Conclusion: The LncRNA GAS5 contributes to SMC survival during AAA formation. Thus, GAS5 might serve as a novel target against AAA.

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“…This up-regulating trend in KB/VIN diminished the functional inhibitory potency of caffeic acid, resulting in weaker MDR reversing effects. Previous research has revealed that the oxidative stress might have a role in the regulation of P-gp expression [43]. As caffeic acid exhibited significant ROS-related anti-oxidant effects, the influence of caffeic acid on ROS production in KB/VIN cell line was performed.…”

Section: Discussionmentioning

confidence: 99%

Caffeic Acid Attenuates Multi-Drug Resistance in Cancer Cells by Inhibiting Efflux Function of Human P-Glycoprotein

et al. 2020

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Multidrug resistance (MDR) is a complicated ever-changing problem in cancer treatment, and P-glycoprotein (P-gp), a drug efflux pump, is regarded as the major cause. In the way of developing P-gp inhibitors, natural products such as phenolic acids have gotten a lot of attention recently. The aim of the present study was to investigate the modulating effects and mechanisms of caffeic acid on human P-gp, as well as the attenuating ability on cancer MDR. Calcein-AM, rhodamine123, and doxorubicin were used to analyze the interaction between caffeic acid and P-gp, and the ATPase activity of P-gp was evaluated as well. Resistance reversing effects were revealed by SRB and cell cycle assay. The results indicated that caffeic acid uncompetitively inhibited rhodamine123 efflux and competitively inhibited doxorubicin efflux. In terms of P-gp ATPase activity, caffeic acid exhibited stimulation in both basal and verapamil-stimulated activity. The combination of chemo drugs and caffeic acid resulted in decreased IC50 in ABCB1/Flp-InTM-293 and KB/VIN, indicating that the resistance was reversed. Results of molecular docking suggested that caffeic acid bound to P-gp through GLU74 and TRY117 residues. The present study demonstrated that caffeic acid is a promising candidate for P-gp inhibition and cancer MDR attenuation.

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The effects of ultrasound exposure on P-glycoprotein-mediated multidrug resistance in vitro and in vivo

Cited by 18 publications

References 55 publications

Very low intensity ultrasounds as a new strategy to improve selective delivery of nanoparticles-complexes in cancer cells

Very low intensity ultrasounds as a new strategy to improve selective delivery of nanoparticles-complexes in cancer cells

Long noncoding RNA GAS5 induces abdominal aortic aneurysm formation by promoting smooth muscle apoptosis

Caffeic Acid Attenuates Multi-Drug Resistance in Cancer Cells by Inhibiting Efflux Function of Human P-Glycoprotein

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