Reversal of 5-fluorouracil resistance by EGCG is mediate by inactivation of TFAP2A/VEGF signaling pathway and down-regulation of MDR-1 and P-gp expression in gastric cancer

Tang, Hua; Zeng, Li‐Si; Wang, Jiahong; Zhang, Xiangliang; Ruan, Qiang; Wang, Jin; Cui, Shuzhong; Yang, Dian

doi:10.18632/oncotarget.20666

Cited by 58 publications

(43 citation statements)

References 42 publications

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“…Studies have confirmed that chemotherapy resistance of cancer cells may also be caused by multi-drug resistance gene (MDR-1) and its encoded protein P-gp. 35 Our previous studies have also confirmed that emodin affected the expression of MRP and P-gp expression levels. P-gp, encoded by MDR, is a transmembrane protein and belongs to the ATP-binding cassette transporter protein superfamily.…”

Section: Dovepresssupporting

confidence: 59%

<p>Emodin Reverses Gemcitabine Resistance of Pancreatic Cancer Cell Lines Through Inhibition of IKKβ/NF-κB Signaling Pathway</p>

Tong¹,

Huang²,

Chen³

et al. 2020

OTT

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Background: Pancreatic cancer is one of the most malignant tumors, and gemcitabine has been considered as the standard treatment and been widely utilized as a first-line drug for advanced pancreatic cancer, but gemcitabine-resistance always occurs after a short period of treatment. Methods: Two pancreatic cancer cell lines Panc-1 and MIA-PaCa-2 were used as the study subject and their gemcitabine-resistant cells were established. Both drug-resistant cells were divided into four groups: blank, emodin, gemcitabine, and emodin+gemcitabine. Cell viability was detected by MTT assay. Flow cytometry was performed to detect cell apoptosis rate and P-gp function. Quantitative real-time polymerase chain reaction and Western blotting were used to detect Survivin, XIAP, Caspase-9/3, NF-κB p65, IKKβ and IκB-α mRNA/ protein expressions, respectively. Electrophoretic mobility shift assay (EMSA) was performed to detect NF-κB binding activity. Rhodamine 123 efflux assay was used to detect P-gp function. Results: Emodin could inhibit cell activity in all cell lines. Both emodin and gemcitabine can significantly increase the apoptosis rate, and the combination of the two drugs can further significantly increase the apoptosis rate in normal pancreatic cancer cell lines. In both drugresistant pancreatic cancer cell lines, it can be observed that although gemcitabine can increase the apoptosis rate, the effect of promoting apoptosis is significantly lower than that of emodin; the drug combination can still significantly increase the apoptosis rate on the basis of emodin alone. Emodin can significantly reduce the mRNA and protein expression levels of Survivin, XIAP, NF-κB, and IKKβ, and significantly increase the mRNA and protein expression levels of Caspase-3/9 and IκB-α. Emodin significantly reduced NF-κB activity and emodin significantly promoted P-gp fluorescence intensity from Rhodamine 123 efflux assay. Conclusion: Emodin inhibits the expression of IKKβ, thereby inhibiting the expression and activity of downstream NF-κB, and inhibits P-gp function at the same time, ultimately achieving the purpose of reversing the drug-resistance of pancreatic cancer cell lines.

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Section: Dovepresssupporting

confidence: 59%

<p>Emodin Reverses Gemcitabine Resistance of Pancreatic Cancer Cell Lines Through Inhibition of IKKβ/NF-κB Signaling Pathway</p>

Tong¹,

Huang²,

Chen³

et al. 2020

OTT

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“…Interestingly, this modulation was reversible. Tang and coworkers found that EGCG suppressed the MDR-1 expression in resistant cells (Tang et al, 2017). The study by Zhu and coworkers revealed that tea polyphenol could improve the uptake of 99mTc-tetrofosmin (a substrate for P-gp) in MCF-7/Adr cells (Zhu et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

The favourable effect of catechin in electrochemotherapy in human pancreatic cancer cells

et al. 2018

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Until recently, green tea polyphenols were considered strong antioxidants. However, the latest reports have revealed that bioflavonoids can play a multiple role in anticancer therapy, including the inhibition of cell proliferation and generation of the oxidative stress in a dose-dependent manner. The presented research was designed to examine the potential of the green tea (±)-catechin as a reinforcement of the electrochemotherapy (ECT) with cisplatin in pancreatic cancer in vitro. The study was performed on two cell lines of the pancreatic ductal adenocarcinoma (PDA) - parental EPP85-181P and multidrug-resistant EPP85-181RNOV. Prior to the ECT protocol the cells were preincubated with high or low concentration of catechin for 2 or 24 hours, respectively. We assessed the influence of preincubation on the cisplatin toxicity with and without electroporation (EP), the electrosensitivity of PDA cell lines and the uptake of the daunorubicin and propidium iodide. Additionally, we evaluated the antioxidative properties of catechin by the measurement of the ROS-related fluorescence and the immunoreactivity of the oxidative stress-related enzymes superoxide dismutase (SOD2) and glutathione S-transferase (GST). We found that co-treatment with catechin can firmly enhance the efficacy of electroporation with cisplatin in vitro. More favorable effect was obtained for 2-hour incubation, which indicates the involvement of the transcriptional-independent mechanisms of catechin action. The effect may be partially explained by the increased oxidative stress level, which was higher in multidrug-resistant cells. However, further studies on cisplatin-catechin interplay and the thorough examination of the catechin-cell membrane interaction need to be performed.

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“…Human gastric adenocarcinoma cell line (SGC-7901), maintained in the Surgical Laboratory at Guangzhou Medical University, and the MDR variants SGC-7901/5-FU and SGC-7901/DDP were obtained and maintained in laboratory conditions as described previously [16,17]. Wound healing assay Cells were seeded into six-well plates and transfected with the negative control siRNA-NC or siRNA-XLOC_006753 for 36 h. Then, the cells were serum-starved for 22 h and replenished with 10% fetal bovine serum RPMI-1640 medium.…”

Section: Methodsmentioning

confidence: 99%

Long Non-Coding RNA XLOC_006753 Promotes the Development of Multidrug Resistance in Gastric Cancer Cells Through the PI3K/AKT/mTOR Signaling Pathway

Zeng

Liao

Zou

et al. 2018

Cell Physiol Biochem

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Background/Aims: The development of multidrug resistance (MDR), which results in disease recurrence and metastasis, is a crucial obstacle to successful chemotherapy for patients with gastric cancer (GC). Long non-coding RNAs (lncRNAs) have been found to play various roles in cancer. This study aimed to investigate the effect of XLOC_006753 on the development of MDR in GC cells. Methods: The expression levels of XLOC_006753 in GC patients and MDR GC cell lines (SGC-7901/5-FU and SGC-7901/DDP cell line) were assessed by qRT-PCR. Statistical analyses were conducted to determine the relationship between XLOC_006753 expression and clinical features and to assess the prognostic value of XLOC_006753 for overall survival and progression-free survival. Then, a CCK-8 assay was used to detect cell proliferation ability and chemosensitivity. Flow cytometry was used to detect cell cycle and cell apoptosis. A wound-healing assay and transwell assay were used to detect cell migration. The expression of markers for MDR, G1/S transition, epithelial–mesenchymal transition (EMT) and PI3K/ AKT/mTOR signaling pathway were examined by western blot. Results: XLOC_006753 was highly expressed in GC patients and MDR GC cell lines (SGC-7901/5-FU and SGC-7901/DDP cell lines), and its high expression was positively associated with metastasis, TNM stage, tumor size, and poor survival in GC patients. Moreover, XLOC_006753 was an independent prognostic biomarker of overall survival and progression-free survival for gastric cancer patients. Knocking down XLOC_006753 in the two MDR GC cell lines significantly inhibited cell proliferation, cell viability, cell cycle G1/S transition, and migration. XLOC_006753 knockdown also promoted apoptosis. Furthermore, western blots showed that XLOC_006753 knockdown decreased some markers of MDR, G1/S transition, and EMT expression, while increasing caspase9 expression and inhibiting the PI3K/AKT/mTOR signaling pathway in SGC-7901/5-FU and SGC-7901/DDP cells. Conclusion: High expression of XLOC_006753 promoted the development of MDR, which was activated by the PI3K/AKT/mTOR pathway in GC cells.

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Reversal of 5-fluorouracil resistance by EGCG is mediate by inactivation of TFAP2A/VEGF signaling pathway and down-regulation of MDR-1 and P-gp expression in gastric cancer

Cited by 58 publications

References 42 publications

<p>Emodin Reverses Gemcitabine Resistance of Pancreatic Cancer Cell Lines Through Inhibition of IKKβ/NF-κB Signaling Pathway</p>

<p>Emodin Reverses Gemcitabine Resistance of Pancreatic Cancer Cell Lines Through Inhibition of IKKβ/NF-κB Signaling Pathway</p>

The favourable effect of catechin in electrochemotherapy in human pancreatic cancer cells

Long Non-Coding RNA XLOC_006753 Promotes the Development of Multidrug Resistance in Gastric Cancer Cells Through the PI3K/AKT/mTOR Signaling Pathway

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