RNAi-based Knockdown of Multidrug Resistance-associated Protein 1 is Sufficient to Reverse Multidrug Resistance of Human Lung Cells

Shao, Shihe; Cui, Tingting; Zhao, Wei; Zhang, Weiwei; Xie, Zhenli; Wang, Chang-He; Jia, Hong-Shuang; Liu, Qian

doi:10.7314/apjcp.2014.15.24.10597

Cited by 7 publications

(7 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is possible that an increase in MRP1-mediated efflux of anti-neoplastic agents reduces the intracellular concentration, and thereby decreases the therapeutic efficacy of the agents. RNA interference-based knockdown of MRP1 reversed MDR efficiently by decreasing the efflux ability and increasing the DDP-induced apoptosis in A549/DDP cells (70). These studies provided a solid ground for the clinical use of the MRP1 inhibitor for the treatment of NSCLC patients with enhanced expression of MRP1.…”

Section: Discussionmentioning

confidence: 79%

Clinical relevance of the multidrug resistance‑associated protein�1 gene in non‑small cell lung cancer: A systematic review and meta‑analysis

Wong

Zhou

et al. 2018

Oncol Rep

View full text Add to dashboard Cite

The multidrug resistance‑associated protein 1 (MRP1) gene has been found to be consistently overexpressed in the majority of patients with non‑small cell lung cancer (NSCLC). MRP1 is known for its ability to actively decrease intracellular drug concentration, limiting the efficacy of cancer chemotherapy; however, data on the clinical relevance of MRP1 is inconclusive. In the present meta‑analysis, all available published data were combined to provide an updated view on the clinicopathological relevance of MRP1 in patients with NSCLC. A systematic search was conducted to obtain relevant studies published in English, Chinese and Japanese databases. All data from patients with NSCLC who underwent testing for MRP1, by either immunohistochemistry or reverse transcription‑polymerase chain reaction, were extracted and combined for further analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each selected study, with either the fixed‑effects model or the random‑effects model where appropriate. The quality of methodology, heterogeneities and publication bias of the included articles were also analyzed. A total of 36 clinical studies involving 3,278 patients were included in the study. It was found that the increased expression of the MRP1 gene was associated with the following subgroups of patients: Non‑smokers vs. smokers (OR, 2.54; 95% CI, 1.17‑5.54; P=0.019); adenocarcinoma vs. squamous cell carcinoma (OR, 1.58; 95% CI, 1.16‑2.17; P=0.004); clinical stage III‑IV vs. stage I‑II (OR, 1.36; 95% CI, 1.11‑1.66; P=0.003); lymph node metastases (OR, 1.32; 95% CI, 1.09‑1.61; P=0.005); poor response to chemotherapy (OR, 0.41; 95% CI, 0.23‑0.72; P=0.002) and reduced 3‑year survival rate (OR, 0.40; 95% CI, 0.23‑0.68; P=0.001). In conclusion, the findings from this study suggest that increase in MRP1 gene expression is associated with being a non‑smoker, adenocarcinoma, advanced clinical stages and a poor response to chemotherapy in patients with NSCLC. The results from the most extensive and updated data on MRP1 support the requirement for continued investigation into the potential use of MRP1 as a biomarker/clinical indicator for NSCLC.

show abstract

Section: Discussionmentioning

confidence: 79%

Clinical relevance of the multidrug resistance‑associated protein�1 gene in non‑small cell lung cancer: A systematic review and meta‑analysis

Wong

Zhou

et al. 2018

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…β-actin and U6 were used as endogenous controls. Using the Ct values obtained by the analysis software, the relative expression levels of EGR1 and MRP1 mRNAs, lncRNA HOTAIR, and miR-6807-3p were calculated through the 2 -ΔΔCt algorithm [26][27][28]. The primers used in PCR are shown in Table 4.…”

Section: Real-time Rt-pcr Analysismentioning

confidence: 99%

“…The cells were collect in EP tubes containing 10 μg/mL Rho-123 and incubated for 30 minutes at 37 °C in a 5% CO 2 cell incubator. Flow cytometry was used to measure the uorescence intensity and emission wavelength of Rho-123 in cells with excitation wavelengths of 488 nm and 530 nm [26]. The subtraction of the uorescence retained from the total uorescence is the uorescence index of Rho-123.…”

Section: Flow Cytometry To Determine the Drug E Ux Of Rho-123mentioning

confidence: 99%

“…After 5 hours of incubation, 180 μL of DMSO was added to each well. After incubation at 37 °C for 24 hours, the absorbance was measured at 570 nm using a microplate reader (TECAN, Switzerland) [26,28].…”

Section: Drug Sensitivity Evaluation Via Mtt Assaymentioning

confidence: 99%

“…fetal bovine serum (FBS; Biological Industries Israel Bei-Haemek Ltd., Israel), 100 U/mL of penicillin sodium, and 100 μg/mL of streptomycin sulfate (Sangon Biotech Shanghai, China) at 37 °C in a humidi ed atmosphere of 5% CO2 (Thermo Electron, USA) [26].…”

mentioning

confidence: 99%

See 2 more Smart Citations

Effect of EGR1-Mediated LncRNA HOTAIR on MRP1 Gene Expression and MDR in Lung Cancer

Zhu

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Multi-drug resistance-associated protein 1 (MRP1) plays critical roles in the multi-drug resistance (MDR) of cancer cells, and its expression is regulated by several transcription factors. However, the effects of EGR1 on MRP1 expression and MDR in lung cancer cells remain unknown.Methods: The expression of Transcription factors EGR1 and lncRNA HOTAIR in Non-small cell lung cancer were detected by using qRT-PCR, at the same time, Western Blot was used to detect the expression of transcription factor EGR1. MTT assay, Flow Cytometry and Observation with laser confocal microscope assay were used to explore the role of EGR1 and lncRNA HOTAIR in Non-small cell lung cancer cells. ChIP PCR assay and Luciferase reporter assays were used to demonstrate the molecular biological mechanism of EGR1 and lncRNA HOTAIR in Non-small cell lung cancer.Results: We found that EGR1 could bind to the MRP1 promoter at site -53/-42 bp and thereby regulate MRP1 expression. EGR1 knock-down reduced MRP1 expression, while EGR1 overexpression increased it. Knockdown of EGR1 increased the drug sensitivity to 5-Fluorouracil (5-FU), Toosendanin (TSN), and cisplatin (DDP), reduced the efflux ability of Rho-123, and induced apoptosis of drug-resistant lung cancer cells A549/DDP, while EGR1 overexpression had the opposite effects. Further, we demonstrated that lncRNA HOTAIR mediated the effects of EGR1 on MRP1 and MDR via sponging of miR-6807-3p. Moreover, we showed that miR-6807-3p exerts its function by targeting the EGR1 3'UTR. Conclusions: We revealed the role and molecular mechanisms of the novel HOTAIR/miR-6807-3p/EGR1 axis in the regulation of MRP1 expression and MDR in lung cancer cells. Our findings identify EGR1 as a potential biomarker and therapeutic target for MDR in human lung cancer.

show abstract

Cisplatin-mediated c-myc overexpression and cytochrome c (cyt c) release result in the up-regulation of the death receptors DR4 and DR5 and the activation of caspase 3 and caspase 9, likely responsible for the TRAIL-sensitizing effect of cisplatin

Zhu

Zhang²,

Wang³

et al. 2015

Med Oncol

View full text Add to dashboard Cite

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) reverses multidrug resistance (MDR) and induces apoptosis in MDR gastric carcinoma cells. In our previous study, cisplatin proved to be a sensitizing agent for TRAIL. To study the synergistic effects of cisplatin and TRAIL, we investigated the mechanism by which TRAIL reverses multidrug resistance, the role of c-myc in modulating the death receptors DR4 and DR5 and the relationship between cisplatin and cytochrome c (cyt c) release in SGC7901/VCR and SGC7901/DDP cells. We found that after treatment with TRAIL, the DNA-PKcs/Akt/GSK-3β pathway, which is positively correlated with the levels of MDR1 and MRP1, was significantly inhibited and that this tendency can be abolished by Z-DEVD-FMK (a specific caspase 3 inhibitor). We also found that suppression of c-myc by siRNA reduced the expression of DR4 and DR5 and that transfection with a pAVV-c-myc expression vector increased the expression of DR4 and DR5. Moreover, cisplatin increased the expression of c-myc in the presence of TRAIL, and there is a clear increase in cyt c release from mitochondria with the increasing concentrations of cisplatin. Meanwhile, the intrinsic death receptor pathway of caspase 9, as well as the common intrinsic and extrinsic downstream target, caspase 3, was potently activated by the release of cyt c. Together, we conclude that in TRAIL-treated MDR gastric carcinoma cells, cisplatin induces the death receptors DR4 and DR5 through the up-regulation of c-myc and strengthens the activation of caspases via promoting the release of cyt c. These effects would then be responsible for the TRAIL sensitization effect of cisplatin.

show abstract

RNAi-based Knockdown of Multidrug Resistance-associated Protein 1 is Sufficient to Reverse Multidrug Resistance of Human Lung Cells

Cited by 7 publications

References 26 publications

Clinical relevance of the multidrug resistance‑associated protein�1 gene in non‑small cell lung cancer: A systematic review and meta‑analysis

Clinical relevance of the multidrug resistance‑associated protein�1 gene in non‑small cell lung cancer: A systematic review and meta‑analysis

Effect of EGR1-Mediated LncRNA HOTAIR on MRP1 Gene Expression and MDR in Lung Cancer

Cisplatin-mediated c-myc overexpression and cytochrome c (cyt c) release result in the up-regulation of the death receptors DR4 and DR5 and the activation of caspase 3 and caspase 9, likely responsible for the TRAIL-sensitizing effect of cisplatin

Contact Info

Product

Resources

About

RNAi-based Knockdown of Multidrug Resistance-associated Protein 1 is Sufficient to Reverse Multidrug Resistance of Human Lung Cells

Cited by 7 publications

References 26 publications

Clinical relevance of the multidrug resistance‑associated protein�1 gene in non‑small cell lung cancer: A systematic review and meta‑analysis

Clinical relevance of the multidrug resistance‑associated protein�1 gene in non‑small cell lung cancer: A systematic review and meta‑analysis

Effect of EGR1-Mediated LncRNA HOTAIR on MRP1&nbsp;Gene Expression and MDR in Lung Cancer

Cisplatin-mediated c-myc overexpression and cytochrome c (cyt c) release result in the up-regulation of the death receptors DR4 and DR5 and the activation of caspase 3 and caspase 9, likely responsible for the TRAIL-sensitizing effect of cisplatin

Contact Info

Product

Resources

About

Effect of EGR1-Mediated LncRNA HOTAIR on MRP1 Gene Expression and MDR in Lung Cancer