Expression of Stat3 and Notch1 is associated with cisplatin resistance in head and neck squamous cell carcinoma.
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.
Gu
Feng
F
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.
Ma
Yongjie
Y
Zhang
Zuping
Z
Zhao
Jinghui
J
Kobayashi
Hisayuki
H
Zhang
Lun
L
Fu
Li
L
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000188:drug therapy*; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006258:Head and Neck Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D051881:Receptor, Notch1 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction
D000970:Antineoplastic Agents; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D002945:Cisplatin