WP1066 Sensitizes Oral Squamous Cell Carcinoma Cells to Cisplatin by Targeting STAT3/miR-21 axis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-05

AUTHORS

Xuan Zhou, Yu Ren, Aiqin Liu, Rui Jin, Qingping Jiang, Yuanyuan Huang, Lingping Kong, Xudong Wang, Lun Zhang

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. More... »

PAGES

7461

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep07461

DOI

http://dx.doi.org/10.1038/srep07461

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1045866285

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25514838


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