The Expression Of STAT3 And Notch1 Were Correlated To Chemotherapy Resistance In Human Head And Neck Squamous Cell Carcinoma

Objective:Chemotherapy was the key pathway to complex therapy and chemotherapy effect was greatly improved with the development of novel chemo-drugs. The cancer cell resistance to chemotherapy can decide it's destine. The current study will explore the STAT3 and Notch1 expression level in head and neck squamous cell carcinoma and its sensitivity to cisplatin treatment.Methods:Twenty-eight fresh specimens of head and neck squamous cell carcinoma were collected for primary cell culture. Five chemotherapy drugs (including paclitaxel, cisplatin,5-FU, boanmycin hydrochloride, navelbine) sensitivity of tumor cells were detected by Collagen Gel Droplet Embedded Culture-Drug Sensitivity Test (CD-DST). CD-DST was conducted to examine cancer cell sensitivity to chemotherapy and Scion Image soft wear was used to calculate the survival rate of the treated cancer cells. The expression of Notch1 and STAT3 in head and neck squamous cell carcinoma, normal squamous epithelium, and tongue squamous cell carcinoma Tb3.1 cells was detected by immunohistochemistry or immuocytochemistry assay. Tb3.1 tongue cancer cell was treated with STAT3 and Notchl inhibitor separately and its sensitivity to cisplatin was measured.Results:In total 28 cases of head and neck squamous cell carcinoma, the success rate of CD-DST was 89.2%(25/28cases); Results of drug sensitivity test indicated that the cancer cells from different patients have significant different sensitivity to anti-cancer drugs; There was a high correlation between the results of CD-DST and clinical response(r=-0.542,p=0.016.The positive rate of STAT3 and Notchl were significantly higher in head and neck squamous cell carcinoma than in normal squamous epithelium (P<0.001), and it was negatively correlated to ciaplatin-sensitivity (P<0.01);There was no difference in absorbance between control and STAT3 or Notchl inhibitor group (P>0.05), while the absorbance was significantly higher in single cisplatin group than in STAT3 or Notch1 inhibitor group with cisplatin (P<0.05).Conclusions:CD-DST has high success rate and will be very useful in screening sensitive drugs for patients to guide the clinical individual chemotherapy. Notch1 and STAT3 expression were negatively correlated to cispaltin-sensitivity of head and neck squamous cell carcinoma, and could be used to predict cisplatin-sensitivity. STAT3 or Notchl inhibitor can enhance cispaltin-sensitivity of Tb3.1 cells via blocking STAT3 and Notchl signaling.