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Effects of Tyrosine Kinase Etk/BMX on the Radiosensitivity of Nasopharyngeal Carcinoma

Author: ZhangZhenHua
Tutor: ZhangJian；GuoLinLang
School: Southern Medical University,
Course: Oncology
Keywords: Nasopharyngeal Tyrosine kinase Radiation Apoptosis Protein Etk / BMX
CLC: R739.63
Type: Master's thesis
Year: 2008
Downloads: 43
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Abstract

Background nasopharyngeal carcinoma (nasopharyngeal carcinoma, NPC) is China's southern high tumor incidence obvious race area and family area accumulation phenomenon. It is estimated that the world 80% of NPC in China, most of which is located in Guangdong and the surrounding areas. Nasopharyngeal carcinoma is the most common malignant tumor of the Department of Otolaryngology, accounting for 78.08% of head and neck cancer. Their age of onset than other types of cancer in young, aged 30-50 up. The multiple men than women, the male to female ratio of 3:1. Early nasopharyngeal cancer cure rate of up to 70%, while the 5-year survival rate of the patients with advanced 8% to 10%. The nasopharyngeal has become a serious threat to the life and health of the people of our country ten malignant one. The nasopharyngeal mostly squamous cell carcinoma, radiotherapy treatment. Some patients with nasopharyngeal carcinoma tumor recurrence, mainly because of cancer cells to radiation resistant, the specific mechanism is not very clear. Impact many factors radiosensitivity of tumor cells, apoptosis is one of the important factors. Since 1972, Kerr found naturally occurring apoptosis phenomenon, people continue to deepen their understanding of, and have been discovered inhibitor of apoptosis gene bcl-2 and apoptosis activation gene p53 and a series of apoptosis regulatory genes, and found that these genes can involved in the regulation of the cell cycle changes. Endothelial / epithelial cell tyrosine kinase (The of endothelial / epithelial tyrosine kinase Etk / BMX) is a protein tyrosine kinase (Bruton's tyrosine kinase, Btk) family. Etk is the only distribution not only in hematopoietic and lymphoid cells, the non-receptor-like tyrosine kinase expression also epithelial tumor cells and vascular endothelial cells. The foreign scholars earliest findings in prostate and breast cancer: high expression of wild-type Etk can significantly inhibit apoptosis in cancer cells. Studies have shown that in NPC Etk appear abnormally high expression in NPC cells. The study was designed to Etk / BMX stable high expressing cell line (sune-wt), from both in vitro and in vivo studies Etk / BMX radiosensitivity of nasopharyngeal carcinoma cells explore nasopharyngeal radiation resistance The mechanism provides experimental evidence. Objective To study the tyrosine kinase Etk / BMX radiosensitivity of nasopharyngeal carcinoma cells and its possible mechanism. Methods Etk lowest sune-1 as the cells of this strain using Lipofectamine2000 the wild-type tyrosine kinase Etk / BMX expression plasmid pcDNA3.0-Etk import which, after screening expand training successfully established nasopharyngeal carcinoma cell lines express Etk / BMX stable high expressing cell lines sune-wt import empty plasmid pcDNA3.0 transfected cells as a control (sune-vector). X-ray (0,2,4,10,15 Gy) irradiation, MTT assay determination of the surviving fraction of cells (survival fraction, SF); apoptosis rate of flow cytometry, cell cycle, proliferation index and apoptosis. protein p53, bcl-2, bcl-xl and bak changes. The above three groups of cells were subcutaneously inoculated in BALB / Cnu / nu nude observed tumorigenicity case and calculation of tumor volume, tumor volume using a caliper measurements mass long radius R1 and the short radius R2. The calculation formula is: V = 4/3 × π × R1 × R1 × R2. As the tumor to a certain time (21 days) when it is the X-ray irradiation (5Gy) × 5 days. Observe changes in their tumor. SPSS 10.0 for the surviving fraction of the rate of apoptosis, cell cycle, proliferation index, p53, bcl-2 and bcl-xl and bak, factorial analysis of animal experiments using a repeated measures design, LSD pairwise comparisons. Data are mean ± standard deviation. Results, success screened high Etk expression cell lines: use of flow cytometry to detect cell lines sune-1 and sune-wt. the sune-1 expression was 4.6 ± 1.45%; sune-wt expression rate was 75.5 ± 2.34%. Sune-wt group SF were significantly higher: SF the sune-wt group after different doses of X-ray irradiation is higher than sune-sune-vector rather sune-1 sune-vector no statistically significant difference. 3, sune-wt apoptosis rate compared with the control group: after different doses of irradiation the sune-wt apoptosis rate was lower than the negative control and blank control group. Apoptosis after 0,4,10 and 15Gy irradiation with increasing irradiation dose increased, the sune-wt than those of other cell lines is not sensitive in the same dose, apoptosis rate is low, while Sune-1 and Sune-vector no significant difference between 4, sune-wt irradiation group decreased compared with the sune-wt unirradiated group p53, bcl-2 increased bcl-xl, bak no significant change, rather sune-1, sune-vector before and after irradiation of p53, bcl-2, bak no statistics learning differences. 5,0,4,10 Gy irradiation after three cell cycle was not statistically change after 15Gy irradiation the sune-wt apparent S and G2 phase arrest in G1 phase decreased. Proliferation index than those before irradiation after irradiation improve, sune-wt increase more significantly. 6, subcutaneous cells inoculated into the aneurysm results are shown: Sune-wt inoculation the primary success rate of 87.5%, Sune-1 is 50%, Sune-vector of 40%. the sune-wt than higher the sune-vector and sane-1 rate of tumor volume growth in the X-ray irradiation compared with the fast the sune-vector and sane-1 speed, the difference is significant. V. Conclusion In vitro experiments show: Etk / BMX enhanced nasopharyngeal carcinoma cell resistance to radiation, the mechanism may be two ways to achieve S, G2 arrest through the regulation of p53 and bcl-2 expression and caused. In vivo experiments confirmed: Etk / BMX in animals can also be enhanced nasopharyngeal radiation resistance.

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