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Cited by 54MicroRNA in disease regulationCytokine Signaling Pathways and InteractionsHead and Neck Cancer Studies

WP1066 sensitizes oral squamous cell carcinoma cells to cisplatin by targeting STAT3/miR-21 axis

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Zhou, Xuan, Ren, Yu, Liu, Aiqin, Jin, Rui, Jiang, Qingping, Huang, Yuanyuan, Kong, Lingping, Wang, Xudong +1 more·2014·Scientific Reports
DOI 10.1038/srep07461PMC PMC4268632
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Abstract

Accumulating evidence reveals that activation of STAT3 and miR-21 contributes to chemoresistance in multiple tumors. We examined the expression of STAT3 and miR-21 in 43 oral squamous cell carcinoma (OSCC) tumors and classified them into cisplatin sensitive or resistant group. Tca8113 and Tca8113/DDP cells were treated with cisplatin (DDP), WP1066 (STAT3 inhibitor) or in combination. MTT, colony formation, wound healing, 3-D culture and transwell chamber assays were used to evaluate the malignant phenotype of OSCC cells. We evaluated the effect of WP1066 on the expression of STAT3 and miR-21. A Tca8113/DDP OSCC xenograft tumor model was established to evaluate the therapeutic effect of WP1066 in combination with DDP. The expression of STAT3/miR-21 was significantly increased in DDP-resistant OSCC samples and Tca8113/DDP cells compared to its parental cell. Treatment of DDP combined with WP1066 efficiently inhibited Tca8113 and Tca8113/DDP cell proliferation, migration and invasion. STAT3 mediated OSCC cell survival and DDP resistance through upregulating the expression of miR-21 and downregulating miR-21 downstream targets, including PTEN, TIMP3 and PDCD4. WP1066 plus DDP treatment could inhibit Tca8113 and Tca8113/DDP cell growth by inhibiting STAT3 phosphorylation and miR-21 expression. These results indicated that STAT3/miR-21 axis could be a candidate therapeutic target for OSCC chemoresistance.

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  • WP1066, a STAT3 inhibitor, up-regulates PDCD4-protein levels by inhibiting the STAT3/miR21 axis.

    “WP1066, a STAT3 inhibitor also up-regulate the protein levels by inhibiting the STAT3/miR21 axis [97].”

    From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [97]

    The Results section ('WP1066 potentiated DDP efficacy in DDP resistant OSCC cell line in vitro'; page unavailable) reports increased PDCD4 protein and inhibition of the STAT3/miR-21 axis in cisplatin-resistant oral cancer cells treated with WP1066 plus cisplatin. The claim omits the cisplatin combination and cell context; this passage does not establish the stated PDCD4 protein increase with WP1066 alone. (LLM, conf=0.86)

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Authors
Zhou, X., Ren, Y., Liu, A., Jin, R., Jiang, Q., Huang, Y., Kong, L., Wang, X., & Zhang, L.
Affiliations
  • Tianjin Medical University Cancer Institute and Hospital (CN)
  • Tianjin Medical University (CN)
  • Third Affiliated Hospital of Guangzhou Medical University (CN)
Corresponding author
  • Wang, Xudong
  • Zhang, Lun
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2014-12-17
Volume
4
Issue
1
Pages
7461-7461
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/srep07461
PMC
PMC4268632
OpenAlex
W2005500857
Cited by
54
References
37
Citations by year
2026: 1 · 2025: 4 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 5 · 2020: 4 · 2019: 5 · 2018: 7 · 2017: 7 · 2016: 6 · 2015: 7
FWCI
2.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Tianjin Science and Technology Committee (11JCYBJC10800, 12JCYBJC33800)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
Keywords
oral squamous cell carcinoma, cisplatin resistance, chemoresistance, STAT3, miR-21, WP1066, STAT3 inhibitor, combination therapy, PTEN, TIMP-3, PDCD4, cell proliferation, cell migration and invasion, xenograft tumor model
MeSH terms
Animals, Carcinoma, Squamous Cell, Cell Survival, Cisplatin, Female, Humans, Mice, Nude, Mouth Neoplasms, Phosphorylation, Pyridines, Down-Regulation, Up-Regulation, RNA-Binding Proteins, Drug Resistance, Neoplasm, Tissue Inhibitor of Metalloproteinase-3, Tyrphostins, MicroRNAs, Cell Line, Tumor, Cell Proliferation, STAT3 Transcription Factor, Apoptosis Regulatory Proteins, PTEN Phosphohydrolase, Mice, Heterografts

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