Zuping Zhang1, Zhongxin Zhou2, Mingde Zhang3, Neil Gross4, Lili Gong2, Shihong Zhang2, Dapeng Lei5, Qiang Zeng6, Xiaoning Luo7, Guojun Li4, Xuezhong Li8. 1. Department of Otorhinolaryngology, Qilu Hospital of Shandong University, NHC Key Laboratory of Otorhinolaryngology (Shandong University), Jinan, Shandong, China; Department of Otorhinolaryngology, Liaocheng People's Hospital, Liaocheng, Shandong, China. 2. Department of Otorhinolaryngology, Liaocheng People's Hospital, Liaocheng, Shandong, China. 3. Department of Otorhinolaryngology, Liaocheng Dongchangfu People's Hospital, Liaocheng, Shandong, China. 4. Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 5. Department of Otorhinolaryngology, Qilu Hospital of Shandong University, NHC Key Laboratory of Otorhinolaryngology (Shandong University), Jinan, Shandong, China. 6. Department of Hepatobiliary Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. 7. Department of Otolaryngology-Head and Neck Surgery, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China. Electronic address: luoxn_ent@126.com. 8. Department of Otorhinolaryngology, Qilu Hospital of Shandong University, NHC Key Laboratory of Otorhinolaryngology (Shandong University), Jinan, Shandong, China. Electronic address: lxzebyh@163.com.
Abstract
BACKGROUND: Notch1 expression has been reported to be associated with chemotherapy resistance and poor prognosis, but the role of Notch1 in head and neck squamous cell carcinoma (HNSCC) sensitivity to anticancer drugs remains unclear. The aim of this study was to evaluate HNSCC sensitivity to paclitaxel and cisplatin in vitro and the chemotherapeutic response of HNSCC to these two drugs in vivo. METHODS: We used immunohistochemistry to assess Notch1 expression in fresh HNSCC samples treated by PF (cisplatin+5- fluorouracil) and TPF (paclitaxel + cisplatin+5- fluorouracil). We also assessed the sensitivity of two HNSCC cell lines to the Notch1 inhibitor of N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT). The overall and progression-free survival were assessed. RESULTS: High Notch1 expression was significantly associated with paclitaxel resistance (P < 0.01). DAPT increased sensitivity to paclitaxel and cisplatin in vitro (P < 0.05). Compared with patients with Notch1 expression, patients without Notch1 expression were more likely to have a response to neoadjuvant chemotherapy with PF (P < 0.01) or TPF (P < 0.01) and had significantly better overall survival (P < 0.05) and progression-free survival (P < 0.05). Among patients without Notch1 expression (but not among patients with Notch1 expression), those who received TPF had significantly better survival than those who received PF (P < 0.05). CONCLUSION: Taken together, our findings may provide some evidence to partially support the predictive value of Notch1 expression in the therapeutic response to paclitaxel and cisplatin.
BACKGROUND:Notch1 expression has been reported to be associated with chemotherapy resistance and poor prognosis, but the role of Notch1 in head and neck squamous cell carcinoma (HNSCC) sensitivity to anticancer drugs remains unclear. The aim of this study was to evaluate HNSCC sensitivity to paclitaxel and cisplatin in vitro and the chemotherapeutic response of HNSCC to these two drugs in vivo. METHODS: We used immunohistochemistry to assess Notch1 expression in fresh HNSCC samples treated by PF (cisplatin+5- fluorouracil) and TPF (paclitaxel + cisplatin+5- fluorouracil). We also assessed the sensitivity of two HNSCC cell lines to the Notch1 inhibitor of N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT). The overall and progression-free survival were assessed. RESULTS: High Notch1 expression was significantly associated with paclitaxel resistance (P < 0.01). DAPT increased sensitivity to paclitaxel and cisplatin in vitro (P < 0.05). Compared with patients with Notch1 expression, patients without Notch1 expression were more likely to have a response to neoadjuvant chemotherapy with PF (P < 0.01) or TPF (P < 0.01) and had significantly better overall survival (P < 0.05) and progression-free survival (P < 0.05). Among patients without Notch1 expression (but not among patients with Notch1 expression), those who received TPF had significantly better survival than those who received PF (P < 0.05). CONCLUSION: Taken together, our findings may provide some evidence to partially support the predictive value of Notch1 expression in the therapeutic response to paclitaxel and cisplatin.