|
Ovarian cancer, gynecological malignancies, the highest mortality, but its cause is not clear. A large number of epidemiological investigations proved that the occurrence of ovarian cancer with high gonadotropin levels of stimulation and excessive ovulation. GnRH There are many subtypes, mainly regulating the gonadal receptor formation and hormonal function, mainly found in the mammalian GnRH Ⅰ and GnRH II. GnRH and its receptor is highly expressed in hormone-dependent tumors, and play an important role in regulating its growth, such as breast cancer, ovarian cancer, endometrial cancer, prostate cancer, liver cancer. Studies have shown that the targeted application of hormone-related reagents, synthetic GnRH analogues is an efficient and low toxicity anti-tumor agent, has been used in the clinical treatment of ovarian cancer. Therefore, the in-depth study of the GnRH and its receptor function and mechanism of action for the development of ovarian cancer targeted therapies provide a theoretical basis. Systematic differences observed GnRH Ⅰ and GnRH receptor expression in benign and malignant tumors of epithelial ovarian tissue in this study reveals the relationship between the level of both pathological differentiation of ovarian cancer; further observed GnRH analogues on ovarian cancer growth inhibition, to clarify the mechanisms of GnRH agonists increase the effect of chemotherapy, and provide an experimental basis for targeted therapy of ovarian cancer at the molecular level. The first part of GnRH Ⅰ and GnRH receptor expression in ovarian tumors and significance Objective: To observe the GnRH Ⅰ and GnRH receptor expression in benign and malignant tumors of epithelial ovarian tissue differences reveal the relationship between the two with the level of differentiation of ovarian cancer pathology. Methods: Immunohistochemical SP method detected 22 cases of benign ovarian epithelial tumors and 39 cases of ovarian cancer in GnRH Ⅰ and GnRH receptor expression. Results: 1 of GnRH I and GnRH receptor localization and distribution: epithelial ovarian tumor tissue by immunohistochemical SP staining specificity. Ovarian epithelial tumors GnRH Ⅰ positive products are mostly located in the cytoplasm and cell membrane, nucleus positive products; GnRH receptor-positive epithelial ovarian tumor tissue products are mostly located in the cytoplasm and cell membrane, nucleus positive products. Relationship between GnRH I in the expression of epithelial ovarian tumors and tissue differentiation: benign ovarian epithelial tumors of GnRH Ⅰ positive expression rate (54.5%) lower than ovarian cancer GnRH I expression (79.5%), the difference was statistically significant ( X2 = 4.21, P lt; 0.05); the pathological grading GnRH Ⅰ G1, ovarian cancer tissue positive rate (50%) is lower than the G2 stage ovarian cancer tissue GnRH Ⅰ positive rate (91.7%), the difference was statistically significant (X2 = 5.04, P lt; 0.05); and G3 grade ovarian cancer tissues GnRH Ⅰ positive expression rate (93.3%), and G2 stage ovarian cancer tissues express the difference was not statistically significant (X2 = 0.03, P gt; 0.05). The relationship between the expression of GnRH receptors in epithelial ovarian tumors and tissue differentiation: benign ovarian epithelial tumors GnRH receptor-positive rate (81.8%) higher than that of ovarian cancer (53.8%) was statistically significant ( X2 = 4.77, P lt; 0.05); the G1, pathological grade ovarian cancer tissues GnRH receptor-positive rate (16.7%) is lower than the the of G2 stage ovarian cancer tissue GnRH receptor-positive rate (58.3%), a statistically significance (X2 = 4.44, P lt; 0.05); G3 grade ovarian cancer tissues GnRH receptor positive expression rate (80.0%), with the G2 stage ovarian cancer tissues express the difference was not statistically significant (X2 = 1.50, P gt; 0.05). Conclusion: 1 GnRH Ⅰ and GnRH receptor in ovarian benign and malignant epithelial tumor tissue were expressed GnRH / paracrine regulation system exists in epithelial ovarian tumor tissue. The 2 GnRH Ⅰ and GnRH receptor expression in ovarian cancer Histopathological grading. With the differentiation increased level of GnRH I and GnRH receptor expression levels increased, suggesting that ovarian cancer GnRH I and GnRH receptor and ovarian cancer proliferation, invasion and poor prognosis. The second part of the GnRH agonist triptorelin inhibitory effect on the growth of ovarian cancer OVCAR3 purpose: To observe the GnRH agonist triptorelin on ovarian cancer cell growth inhibition and to explore the mechanism of induction of apoptosis. MTT assay method: use different concentrations of triptorelin stimulation of ovarian cancer cells OVCAR3 cell proliferation activity. Using RT-PCR method for detection of triptorelin Caspase-3 expression of apoptosis-related factors in ovarian cancer cells OVCAR3. Results: 1 triptorelin OVCAR3 ovarian cancer cell proliferation activity: MTT results showed ,10-7mol / l concentrations of triptorelin role in cell after 24h, proliferation inhibition rate (41.07 ± 0.43)%, with the significant increase of drug concentration (10-6mol / L ,10-5 mol / L ,10-4mol / L ,10-3 mol / L ,10-2mol / l), the inhibition rate is gradually increased, respectively (50.56 ± 0.76)% (69.86 ± 1.05)%, (65.43 ± 0.87)% and (62.09 ± 1.24)%, (58.69 ± 0.87)%; triptorelin highest inhibition rate to the song of the 10-5mol / l concentration, significant ( P lt; 0.05); 10-5mol / l concentrations of triptorelin role in cell 24h, 48h after 72 hours, the proliferation inhibition rate (69.86 ± 1.08)%, (58.69 ± 0.98)%, (48.56 ± 1.02%), the role of time in 24h, the inhibition rate highest statistical significance (P lt; 0.05). 2 triptorelin on ovarian cancer Caspase-3 expression of apoptosis-related factors ① 10-4mol / l ,10-5 mol / l ,10 mol / l concentrations of triptorelin role OVCAR3 cells after 24h, Caspase -3 OD values ??(0.51 ± 0.04), (0.71 ± 0.07), (0.41 ± 0.04), with the control group cells OD values ??(0.33 ± 0.02) compared to Caspase-3 in the triptorelin in 10 -5mol / l concentration, the highest expression level was statistically significant (F = 42.028, P lt; 0.05); ② 10-4mol / l ,10-5 mol / l ,10-6mol / l concentrations of triptorelin role OVCAR3 cells 48h after the OD value of caspase-3 (0.69 ± 0.07), (1.01 ± 0.08), (0.64 ± 0.08), with the control group cells OD value compared to (0.48 ± 0.04), Caspase-3 in triptorelin 10-5mol / l concentration, the highest expression levels was statistically significant (F = 107.595, P lt; 0.05); ③ The 10-4 mol / l concentrations of triptorelin role OVCAR3 cells. after 48h, Caspase-3 OD value (0.85 ± 0.09), (0.62 ± 0.06), compared to the OD value of control cells (0.34 ± 0.04), Caspase-3 in the 10-4mol / l concentration of the song Triptorelin 24h. highest expression level was statistically significant (F = 47.164, P lt; 0.05); the ④ 10-5 mol / l concentration of triptorelin role in OVCAR3 cells 24h, 48h, Caspase-3's OD values ??(0.85 ± 0.09), (0.64 ± 0.05), compared to the OD value of control cells (0.40 ± 0.06) of Caspase-3 in the 10-5mol / l concentrations of triptorelin role 24h, the expression of highest statistically significant (F = 29.647, P lt; 0.05); ⑤ 10-6 mol / l concentrations of triptorelin role OVCAR3 cells. After 48 hours, the OD value of caspase-3 (0.96 ± 0.08, respectively) , (0.68 ± 0.04), OD value of control cells (0.58 ± 0.04) compared to, Caspase-3 in the 10-4mol / l concentrations of triptorelin role 24h, the highest expression level was statistically significant (F = 48.337, P lt; 0.05). Conclusion: 1 triptorelin GnRH receptor positive ovarian cancer cell growth inhibition. Triptorelin role in ovarian cancer, can induce apoptosis, Caspase-3 expression of apoptosis-related factors increased.
|