WP1066 sensitizes oral squamous cell carcinoma cells to cisplatin by targeting STAT3/miR-21 axis.
WP1066 sensitizes oral squamous cell carcinoma cells to cisplatin by targeting STAT3/miR-21 axis.
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WP1066 通过靶向 STAT3/miR-21 轴使口腔鳞状细胞癌细胞对顺铂敏感
DOI：
10.1038/srep07461
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发表时间：
2014-12-17
影响因子：
4.6
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Zhou X;Ren Y;Liu A;Jin R;Jiang Q;Huang Y;Kong L;Wang X;Zhang L
越来越多的证据表明，STAT 3和miR-21的激活有助于多种肿瘤的化疗耐药性。我们检测了43例口腔鳞状细胞癌（OSCC）中STAT 3和miR-21的表达，并将其分为顺铂敏感组和耐药组。Tca 8113和Tca 8113/DDP细胞用顺铂（DDP）、WP 1066（STAT 3抑制剂）或联合处理。采用MTT法、集落形成法、伤口愈合法、三维培养法和transwell小室法检测细胞恶性表型。我们评估了WP 1066对STAT 3和miR-21表达的影响。建立Tca 8113/DDP口腔鳞癌异种移植瘤模型，评价WP 1066联合DDP的治疗效果。与其亲本细胞相比，STAT 3/miR-21在DDP耐药的OSCC样品和Tca 8113/DDP细胞中的表达显著增加。DDP联合WP 1066能有效抑制Tca 8113和Tca 8113/DDP细胞的增殖、迁移和侵袭。STAT 3通过上调miR-21的表达和下调miR-21下游靶点（包括PTEN、TIMP 3和PDCD 4）介导OSCC细胞存活和DDP抗性。WP1066联合DDP处理Tca 8113和Tca 8113/DDP细胞可通过抑制STAT 3磷酸化和miR-21表达而抑制细胞生长。这些结果表明STAT 3/miR-21轴可能是OSCC化疗耐药的候选治疗靶点。
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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影响因子：
8
作者：
Bourguignon, L. Y. W.;Earle, C.;Wong, G.;Spevak, C. C.;Krueger, K.
通讯作者：
Krueger, K.
影响因子：
4.8
作者：
Chang, Qing;Bournazou, Eirini;Bromberg, Jacqueline
通讯作者：
Bromberg, Jacqueline
Stat3和Notch1的表达与头颈鳞癌顺铂耐药相关
影响因子：
4.2
作者：
Gu, Feng;Ma, Yongjie;Fu, Li
通讯作者：
Fu, Li
影响因子：
11.2
作者：
Leslie, K;Lang, C;Bromberg, J
通讯作者：
Bromberg, J
影响因子：
2.1
作者：
Lam, L;Logan, RM;Luke, C
通讯作者：
Luke, C