The Expressions Of XIAP In Oral Squamous Cell Carcinoma And Its Effect On The Chemotherapeutic Sensitivity Of Tca8113 Cells

Oral squamous cell carcinoma (OSCC) is most common oral cancer,which is a serious threat to human health with a very high incidence and a low survival rate.Nowadays most researchers propose that polycellular organisms maintain homeostasis by the modulation of cell proliferation and apoptosis. If the balance of cell proliferation and apoptosis was lost, the homeostasis would be broken down and some diseases would occur, such as tumor, neural degeneration and autoimmune disease. The inhibitor of apoptosis proteins (IAPs) are a family of intracellular anti-apoptotic proteins with homologous structure and extensive localization in a lot of species. In 1996,XIAP, HIAP-1 and HIAP-2 was firstly identified by Rajcan-Separovic et al. Subsequent studies found XIAP have various effect on tumorigenesis, development and prognosis of tumor. XIAP gene localizes in X chromatosome q25 and XIAP mRNA has 1.5 kb coding region. The relative molecular weight of XIAP is 57kD and its molecular structure is studied clearer than that of any other member. The N-end of XIAP consists of three Baculoviral Inhibitor of apoptosis Repeats (BIR), which are the essential domains for inhibitory action of apoptosis. The C-end of XIAP consists of a RING zinc fingers domain,which functions as ubiquitin ligase E3 and catalyzes self or interactive proteins through ubiquitin proteasome pathway. XIAP generally expresses in most tissue of adults and infants except for peripheral blood lymphocytes. Some experimental results have indicated that XIAP has subcellular localization of perinuclear areas and cytoplasm.Caspases are a series of critical proteases regulating and executing cell apoptosis process,which initiate apoptosis signaling cascade, split constitutive proteins and regulatory proteins and result in cell apoptosis. Studies have shown that XIAP is most potent inhibitor of caspase in the members of IAP family. XIAP could bind to and inhibit caspase-3, caspase-7 and caspase-9 depending on BIRs and catalyze caspases degradation depending on RING zinc fingers. So XIAP could effectively resist apoptosis. XIAP could protect impaired neuron and prevent retrogression of motoneuron.In addition, XIAP could also potentialize postinflammatory reparation effect of endothelial cells.Experiments have indicated XIAP abnormally expresses in multitude neoplasmes, such as prostatic carcinoma, mammary carcinoma, pulmonary carcinoma, The XIAP,as the most potent one of inhibitor of apoptosis IAP)families,up-regulating in many cancer tissues and cells,is thought an important factor cinteibbuted to carcinoma proliferation,transformation and chemoresistance. X linked inhibitor of apoptosis proteins (XIAP), which is expressed at high levels in many tumors, block apoptosis at the core of the apoptotic machinery by inhibiting caspases, confers radioresistance and in some groups of patients, associated with development and progression and dismal prognosis of malignancies.Objective:To investigate the expression of XIAP in oral squamous carcinomas and in cultured chemotherapeutic agent cells in vitro to observe the relationship between the apoptosis and variation of XIAP expression in drug-resistanced cells after chemotherapeutic agent; Methods:XIAP expression was detected by immunohisto-chemistry in 28 cases OSCC tissues and 10 cases of nomal oral mucosa tisues. The Tca8113 cultured by IMDM, and the concentration of pingyangmycin added to Tca8113 cells was increased gradually and continually, which was to induce the pingyangmycin- resistance in Tca8113 cells. The sensitivity of Tca8113 to chemothrapeutical drug and expression of XIAP in varial cells were measured with MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromid) chromatometry and RT-PCR.Results: XIAP expression in 23 of 28 (82.14%) of OSCC,and 3 of 10 (30.0%) of the nomal oral mucosa tisues:The positive rate and expression level of XIAP protein in OSCC were higher than the normal oral mucosa tisues,XIAP expression was significant difference between pathological grades (P<0.05);10 days after cultured by pingyangmycin with the cincentration of Tca8113-1 and Tca8113-10,the IC50 of Tca8113 cell increased from 6.414±0.059μg /ml to 12.758±0.030μg/ml ( P<0.05 ) and18.986±0.150μg /ml(p<0.05)respectively,and the mRNA of XIAP not enhanced obviously;after 30 days,the IC50 increased to 26.302±0.072μg/ml(P<0.01),35.294±0.115μg /ml(p<0.01)respectively,and the mRNA of XIAP increased greatly;and there was a relation between XIAP and the drug- resistance .Conclusions: The positive rate and expression level of XIAP protein in OSCC were higher than the nomal oral mucosa tisues,XIAP expression was significant difference between pathological grades ;XIAP expression could be related to the differentiation and could play possibly important roles in the chemoresistance. ;Tca8113-1or T ca8113-10 can provide an ideal model for multidrug resistance research.At present,the assocition of XIAP expression characteristics with OSCC development was rarely studied,and there is no report on the relation between XIAP and drug-sensitive of OSCC cells yet.so as to study expression characteristics and the effect to drug-sensitive of XIAP in OSCC ,it is significant to illustrate the mechanism of development and drug resistance, and explore the methods of enhancing therapeutic sensitivity of OSCC.