The Effect Of PDTC Inhibition On Circulating Tumor Cells Of Laryngeal Carcinoma And Its Mechanism

PART 1 THE EFFECT OF PDTC INHIBITION ON CIRCULATING TUMOR CELL OF LARYNGEAL CARCINOMAOBJECTIVE: Use of laryngeal carcinoma nude mouse model, Detection the expression of nuclear factor (NF-κB) in laryngeal carcinoma in nude mice . Observate the correlation between nuclear factor (NF-κB) and circulating tumor cells (CTC) of laryngeal carcinoma in nude mice. To investigate the effect of PDTC on circulating tumor cells of laryngocarcinoma in nude mice model.METHODS: 60 4 weeks old BALB / c-nu nude mice were randomly divided into experimental group (20), the control group (20), and Sham group (20).The experimental group is PDTC pretreatment group,Seventh day after inoculation of laryngeal cancer cells ,intraperitoneal administration(0.2～0.3ml) of the final concentration (100mg/kg). The control group is NS group(Equal NS). The Sham group not inoculated carcinoma cells. The Subcutaneous right neck of nude mice inoculated with laryngo carcinoma Hep-2 cells 0.2ml.The PDTC group and control group 40 tumor in nude mice were successfully. When the tumor growth of 8 weeks, mice were sacrificed, remove the tumor tissue and blood. Conventional HE staining of tumor tissue.use CK-19 as markers to detection the expression of circulating tumor cells in laryngeal cancer in nude mice. Immunohistochemical detection of nuclear factor (NF-κB) expression in laryngeal carcinoma, NF-κB will from the cytoplasm to the nucleus when activitied.Thus the tumor cell nuclei stained brown that reflects the activation of NF-κB.RESULTS:1.The expression of Nuclear factor (NF-κB) in laryngeal carcinoma was 65%(26/40).In CTC positive laryngeal carcinoma , the positive rate of NF-κB was 90%(9/10). In CTC negative laryngeal carcinoma, the positive rate of NF-κB was 56.7%(17/30),there was no significant correlation between CTC and the positive rate of NF-κB in laryngeal carcinoma. However,in the NF-κB was activated nude mice model, The positive rate of CTC was 75% (9/12),in the NF-κB was not activated nude mice model, The positive rate of CTC was 3.5%(1/28).There was significant correlation between CTC and the activity of NF-κB in laryngeal carcinoma.2. The PDTC group CTC positive rate was 5%, the Control group CTC positive rate was 45%. CTC positive rate between the two groups were significantly different. (P<0.005)CONCLUSION:1.In laryngeal carcinoma nude mouse model, there was not significantly correlation between circulating tumor cells and the positive rate of NF-κB. But was related to the activity of NF-κB.2.PDTC could inhibit NF-κB in laryngeal carcinoma activation, reduce the incidence of CTC in laryngeal carcinoma in nude mouse model. PART 2 THE MECHANISM OF PDTC INHIBITION ON CIRCULATING TUMOR CELL OF LARYNGEAL CARCINOMAOBJECTIVE: Use laryngeal carcinoma nude mouse model, observed the expression of VEGF-C and MMP-9mRNA in laryngeal carcinoma after PDTC administrated. To investigate the Possible mechanism. To provide new ideas for the clinical treatment of laryngeal cancer.METHODS: 60 4 weeks old BALB / c-nu nude mice were randomly divided into experimental group (20), the control group (20), and Sham group (20).The experimental group is PDTC pretreatment group,Seventh day after inoculation of laryngeal carcinoma cells,intraperitoneal administration(0.2～0.3ml) of the final concentration (100mg/kg). The control group is NS group(Equal NS). The Sham group not inoculated carcinoma cells. The Subcutaneous right neck of nude mice inoculated with laryngo carcinoma Hep-2 cells 0.2ml.The PDTC group and control group 40 tumor in nude mice were successfully. When the tumor growth of 8 weeks, mice were sacrificed, remove the tumor tissue and blood.measured volumeand. use CK-19 as markers to detection the expression of CTC in laryngeal cancer in nude mice. Quantitative PCR to detect the expression of the VEGF-C and the MMP-9mRNA in laryngeal carcinoma.RESULTS:Tumor growth was inhibited in PDTC group. Its volume was Statistically significant with the control group(P<0.01). The expression of VEGF-C and MMP-9mRNA in PDTC group was significantly reduced compared with the control group.CONCLUSION: PDTC could inhibit NF-κB activation in laryngeal carcinoma, reduce the incidence of CTC,the effect may benefit PDTC reduced the ability of laryngeal carcinoma metastasis. The Possible mechanism may be as PDTC inhibit NF-κB activity lead the expression of VEGF-C and MMP-9 decreased, reduced angiogenesis and tumor invasion.