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Inhibiting Effects Of Serms Alone And The Combination With Cisplatin On The Human Tongue Carcinoma Cell Line Tca8113

Posted on:2011-06-11Degree:MasterType:Thesis
Country:ChinaCandidate:J ZhouFull Text:PDF
GTID:2154330338985984Subject:Oral and clinical medicine
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Objective: The human tongue squamous cell carcinoma is a common malignant tumor in oral and maxillofacial areas, ranking the first among the oral squamous cell carcinoma(OSCC). The treatment for OSCC is mainly based on surgery, accompanied with radiotherapy and chemotherapy. The 5-year survival rate is about 48.0 % to 70.9 %, while the major causes of treatment failure are local and regional recurrence. Chemotherapy before surgery can help shrink lesions and postoperative chemotherapy can prevent the spread of lesions. Tamoxifen (TAM) is an estrogen antagonist, which has been applied in clinical practice as the endocrine treatment of breast cancer for many years. Cisplatin (DPP) is a kind of broad-spectrum chemotherapeutic agent, has been used in the chemotherapy of various solid tumors. We compares the combined effect of tamoxifen and cisplatin with the respective effect of tamoxifen or cisplatin on human tongue squamous cell carcinoma Tca8113, examines whether the combined effect is better than their respective effect, and preliminarily discusses its possible mechanism, in order to provide theoretical basis for the chemotherapy of human tongue squamous cell carcinoma.Methods: The human tongue squamous cell carcinoma cell line Tca8113 was cultured in vitro and the expression of estrogen receptor (ER) was detected in Tca8113 through immunocytochemistry staining. The cell growth inhibition was examined by MTT colorimetric assay after TAM and DDP together or respectively addition. The morphological changes of cells in each group were observed with inverted microscope.Results: In the human tongue squamous cell carcinoma Tca8113 cell lines, the expression of ER-αand ER-βwas founded, and the expression of ER-βwas significantly higher than the expression of ER-α. The typical apoptotic cell morphology was observed in TAM group, DDP group and the combined group, which was not occurred in the control group. MTT colorimetric analysis demonstrated that the proliferation of Tca8113 was inhibited in TAM group, DDP group and the combined group. The inhibition rate of each group was counted according to the following formula: inhibition rate(IR)=(1-OD value of experimental group/OD value of control group)×100 %. Twenty four-hour of inhibition rates of TAM in 1 umol/L, 2μmol/L, 5μmol/L and 10μmol/L are 2.83%, 13.38%, 46.67%, 64.76% respectively, while 24-hour of inhibition rates of cisplatin in 0.1μg/ml, 1μg/ml, 5μg/ml and 10μg/ml were 4.69%, 10.27%, 27.19%, 51.37% respectively, with significant proliferation inhibition (P <0.05). And the inhibition of two drugs on human tongue squamous cell carcinoma Tca8113 depends on the time and the dose(P<0.05). After the drugs addition for 24 hours, comparing the combined result of cisplatin(5μg/ml) and tamoxifen(5μmol/L) with the respective result of tamoxifen(5μmol/L, 10μmol/L) or cisplatin(5μg/ml, 10μg/ml), it was found that the cell proliferation inhibition rate of the combined group was greatly higher than that of the two individual groups, with statistically significant difference(P <0.05).Conclusions:1.The expression of ER-αand ER-βcould be detected in human tongue squamous cell carcinoma Tca8113 cell lines, and the expression of ER-βis higher than the expression of ER-α, which means that they play different roles in the occurrence and progress of the human tongue squamous cell carcinoma.2. Tamoxifen and cisplatin can inhibit the tongue cancer cell line Tca8113 proliferation in vitro. When tamoxifen is combined with cisplatin, the inhibition of cell proliferation and cytotoxicity are significantly enhanced. Inhibitation effect of TAM and DDP have a positive correlation with the dose and the time.3. Tamoxifen, cisplatin and the combination of them can all induce cell apoptosis in vitro. One of the mechanisms is that the inhibition of PKC activity and accelerating the secretion of TGF-β1 may cause the inhibition of cell proliferation and apoptosis. The cell apoptosis rate of the combined group is higher than that of the two individual groups, which may be due to the enhanced sensitivity of cells to cisplatin by tamoxifen, thus resulting the enhanced apoptosis.
Keywords/Search Tags:OSCC, ER-α, ER-β, Tamoxifen, Cisplatin
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