NM23-H1 expression of head and neck squamous cell carcinoma in association with the response to cisplatin treatment

被引:14
|
作者
Wang, Yi-Fen [1 ,2 ]
Chang, Chun-Ju [3 ]
Chiu, Jen-Hwey [4 ]
Lin, Chin-Ping [5 ]
Li, Wing-Yin [2 ,6 ]
Chang, Shyue-Yih [1 ]
Chu, Pen-Yuan [1 ,2 ]
Tai, Shyh-Kuan [1 ,2 ]
Chen, Yu-Jen [4 ,5 ,7 ]
机构
[1] Taipei Vet Gen Hosp, Dept Otorhinolaryngol & Head & Neck Surg, Taipei, Taiwan
[2] Natl Yang Ming Univ, Dept Med, Taipei 112, Taiwan
[3] Natl Taiwan Ocean Univ, Dept Food Sci, Keelung, Taiwan
[4] Natl Yang Ming Univ, Inst Tradit Med, Taipei 112, Taiwan
[5] Mackay Mem Hosp, Dept Med Res, Taipei, Taiwan
[6] Taipei Vet Gen Hosp, Dept Pathol, Taipei, Taiwan
[7] Mackay Mem Hosp, Dept Radiat Oncol, Taipei, Taiwan
关键词
Head and neck squamous cell carcinoma (HNSCC); NM23-H1; Metastasis; Cisplatin; Prognosis; METASTASIS SUPPRESSOR NM23-H1; NUCLEOSIDE DIPHOSPHATE KINASE; PROGNOSTIC-SIGNIFICANCE; TUMOR-SUPPRESSOR; MEDIATED APOPTOSIS; P53; GENE; CYCLIN-A; CANCER; SENSITIVITY; GROWTH;
D O I
10.18632/oncotarget.1912
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We recently reported that low NM23-H1 expression of head and neck squamous cell carcinoma (HNSCC) correlated with poor patients' prognosis. Growing evidence has indicated that high tumor NM23-H1 expression contributes to a good response to chemotherapy. Therefore, we investigated the role of NM23-H1 in susceptibility of HNSCC cells to cisplatin and its clinical significance, as well as the in vitro study for validation was performed. Using immunohistochemistry, we analyzed NM23-H1 expression in surgical specimens from 46 HNSCC patients with cervical metastases receiving surgery and adjuvant chemoradiotherapy. Low tumor NM23-H1 expression correlated with locoregional recurrence of HNSCC following postoperative cisplatin-based therapy (p = 0.056) and poor patient prognosis (p = 0.001). To validate the clinical observation and the effect of NM23-H1 on cisplatin cytotoxicity, we established several stable clones derived from a human HNSCC cell line (SAS) by knockdown and overexpression. Knockdown of NM23-H1 attenuated the chemosensitivity of SAS cells to cisplatin, which was associated with reduced cisplatin-induced S-phase accumulation and downregulation of cyclin E1 and A. Overexpression of NM23-H1 reversed these results, indicating the essential role of NM23-H1 in treatment response to cisplatin. NM23-H1 may participate in HNSCC cell responses to cisplatin and be considered a potential therapeutic target.
引用
收藏
页码:7392 / 7405
页数:14
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