The Application Of CD-DST In Head And Neck Squamous Cell Carcinoma

Purpose:The Collagen Gel Droplet Embedded Culture-Drug Sensitivity Test(CD-DST), a advanced chemosensitivity test,can evaluate the efficacy of anticancer drugs exactly. This study was to investigate the different drug sensitivity of patients to anti-cancer drugs in head and neck squamous cell carcinoma by CD-DST and evaluate the clinical usefulness of CD-DST in head and neck squamous cell carcinoma.Then,CD-DST was used to investigate the influence of Notchl expression and activation on the sensitivity to DDP in head and neck squamous cell carcinomas.Methods:1 A total of 28 fresh surgical specimens derived from head and neck squamous cell carcinoma patients who were diagnosed and treated from January 2007 to September 2008 at the Tianjin Medical University Cancer Institute and Hospital were collected;Five anti-cancer drugs(Paclitaxel,DDP,5-Fu,Bleomycin,navelbine) sensitivity of tumor cells were detected by CD-DST;The differences of anti-drug sensitivity between different sexes,ages,lymphatic metastasis,T grade,pathologic grade and preoperative chemotherapy,were analyzed.The relationship between drug sensitivity and preoperative chemotherapy response was analyzed.2 A total of 25 fresh surgical specimens and archived paraffin blocks derived from head and neck squamous cell carcinoma patients who were diagnosed and treated from January 2007 to May 2008 at the Tianjin Medical University Cancer Institute and Hospital were collected;DDP-sensitivity of tumor cells was detected using CD-DST;Cell line of tongue squamous cell carcinoma was recoveried,and creep plates of induction culture cell were collected for immunocytochemistry;The expression of Notchl in head and neck squamous cell carcinoma,normal squamous epithelium,and tongue squamous cell carcinoma Tb3.1 cells were detected by immunohistochemistry or immuocytochemistry;Tb3.1 cells were divided into four groups,and received treatment of DMSO,DAPT,DMSO plus DDP,DAPT plus DDP,respectively.The absorbance of the four groups was detected by CD-DST to evaluate DDP-sensitivity.Results:1 In total 28 cases of head and neck squamous cell carcinoma,the success rate of CD-DST was 89.3%(25/28cases);Results of drug sensitivity test indicated that the cancer cells from different patients have significant different sensitivity to anti-cancer drugs;We found that sensitivity of anti-cancer drugs had no statistically significant differences according to(P＞0.05) the sexes,ages,lymphatic metastasis,T grade, pathologic grade and preoperative chemotherapy.There were difference between the ratio of 5 anti-cancer drugs' sensitivity,and the sensitivity sequence was Paclitaxel(40%)＞DDP(32%)=5-Fu(32%)＞Bleomycin(24%)＞navelbine(20%).There was conformity between the effective of anti-cancer drugs by CD-DST and by the clinical reports; There was a high correlation between the results of CD-DST and clinical response(r=0.624,P＜0.05).2 There was conformity between the effective power of cisplatin by CD-DST (32%) and by the clinical reports(27%-40%);Notchl was positively expressed in head and neck squamous cell carcinoma,and positive signals appeared as brown granules in the cytoplasm.The positive rate of Notchl was significantly higher in head and neck squamous cell carcinoma than in normal squamous epithelium(100% vs.35%,P＜0.001),and it was negatively correlated to DDP-sensitivity(r=-0.705, P＜0.01);Notchl was positively expressed in Tb3.1 cells,and positive signals appeared as brown granules in the cytoplasm;There was no difference in absorbance between DMSO group and DAPT group(155.4±2.3 vs.154.7±1.2,P＞0.05),while the absorbance was significantly higher in DMSO plus DDP group than in DAPT plus DDP(33.9±1.3 vs.26.6±1.1,P＜0.05).Conclusions:1 CD-DST has high success rate and will be very useful in screening sensitive drugs for patients to guide the clinical individual chemotherapy.The were no significant differences of anti-cancer drugs' sensitivity according to the sexes,ages, lymphatic metastasis,T grade,pathologic grade and preoperative chemotherapy. 2 Notchl was intensely expressed in head and neck squamous cell carcinoma; Notchl expression is negatively correlated to DDP-sensitivity of head and neck squamous cell carcinoma,and could be used to predict DDP-sensitivity.DAPT can enhance DDP-sensitivity of Tb3.1 cells via blocking Notchl signaling.