Stat3 和 Notch1 的表达与头颈部鳞状细胞癌对顺铂的耐药性相关。

Expression of Stat3 and Notch1 is associated with cisplatin resistance in head and neck squamous cell carcinoma.

机构信息

Department of Breast Pathology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Breast Cancer Prevention and Therapy of the Ministry of Education, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin 300060, P.R. China.

出版信息

Oncol Rep. 2010 Mar;23(3):671-6. doi: 10.3892/or_00000683.

DOI:10.3892/or_00000683

PMID:20127005

Abstract

Cisplatin is the most important chemotherapeutic agent involved in treatment of head and neck squamous cell carcinoma (HNSCC), but cisplatin resistance in HNSCC is still a serious problem in clinic. The reasons why patients fail chemotherapy are unclear. We examined 25 HNSCC patients who were all tested for cisplatin sensitivity by CD-DST (collagen gel droplet embedded culture-drug sensitivity) method and expression of Stat3 and Notch1. We found that high expression levels of Stat3 and Notch1 were closely associated with cisplatin resistance respectively (P=0.014, P=0.000). In addition, cisplatin resistance of HNSCC was decreased after inhibition of Stat3 or Notch signaling in vitro. Our results provide first evidence that both high Stat3 and Notch1 expression are associated with cisplatin resistance in HNSCC patients, supporting the hypothesis that co-activation of Stat3 and Notch1 by their crosstalk induces the reprogrammed survival pathways in HNSCC responding to chemotherapy.

摘要

顺铂是治疗头颈部鳞状细胞癌（HNSCC）中最重要的化疗药物，但 HNSCC 中的顺铂耐药仍然是临床中的一个严重问题。患者化疗失败的原因尚不清楚。我们检查了 25 例 HNSCC 患者，这些患者均通过 CD-DST（胶原凝胶滴嵌入培养药物敏感性）方法和 Stat3 和 Notch1 的表达进行了顺铂敏感性测试。我们发现 Stat3 和 Notch1 的高表达水平分别与顺铂耐药密切相关（P=0.014，P=0.000）。此外，体外抑制 Stat3 或 Notch 信号通路可降低 HNSCC 的顺铂耐药性。我们的研究结果首次提供了证据，表明 Stat3 和 Notch1 的高表达均与 HNSCC 患者的顺铂耐药性有关，这支持了 Stat3 和 Notch1 通过其相互作用共同激活可导致 HNSCC 对化疗产生重新编程的存活途径的假说。