不同非甾体消炎药抑制人卵巢癌细胞裸鼠种植瘤的研究
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摘要
目的观察非特异性环氧化酶(COX)抑制剂阿司匹林和选择性COX-2抑制剂美洛昔康在卵巢癌荷瘤裸鼠的抗肿瘤效果。方法选择雌性裸鼠,皮下种植人卵巢癌细胞株OVCAR-3或腹膜内种植人卵巢癌细胞株DISS,经阿司匹林(200μg·mL~(-1))或美洛西康(162μg·mL~(-1))治疗,比较荷瘤小鼠的肿瘤增长和生存期。结果与对照组相比较,阿司匹林和美洛西康治疗组的肿瘤生长受到明显抑制。美洛西康治疗组的肿瘤抑制率优于阿司匹林治疗组(P<0.05)。相较于对照组和阿司匹林治疗组,美洛西康治疗组生存期明显延长,而对照组和阿司匹林治疗组裸鼠的生存期并无明显区别。结论选择性COX-2抑制剂美洛西康在抑制卵巢癌细胞增长和腹水方面优于非选择性COX抑制剂,而且更安全。
Objective To investigate the anti-tumor effects of aspirin, non-specific cyclooxygenase(COX) inhibitors, and meloxicam, a selective COX-2 inhibitor, on xenotransplanted ovarian cancer. Methods The female mice xenografted with subcutaneous OVCAR-3 tumors or with intraperitoneal DISS tumors were treated with aspirin(200 ppm in diet, everyday) or meloxicam(162 ppm in diet, everyday). Compare the tumor growth and survival after treatment between them. Results Each of aspirin and meloxicam treatment significantly suppressed the growth of OVCAR-3 tumors xenotransplanted subcutaneously as compared to control. The inhibition rate of OVCAR-3 tumor growth was higher in the meloxicam treatment group than in the aspirin treatment group( P<0.05). Meloxicam treatment significantly prolonged the survival of mice with malignant ascites derived from DISS cells as compared to control and aspirin treatment. There was no significant difference in survival between control and aspirin treatment. Conclusion These results indicated that a selective COX-2 inhibitor produced greater anti-tumor effect against ovarian cancer than a nonselective COX inhibitor and that meloxicam may have a potential of leading to a novel therapeutic strategy against ovarian cancer.
Objective To investigate the anti-tumor effects of aspirin, non-specific cyclooxygenase(COX) inhibitors, and meloxicam, a selective COX-2 inhibitor, on xenotransplanted ovarian cancer. Methods The female mice xenografted with subcutaneous OVCAR-3 tumors or with intraperitoneal DISS tumors were treated with aspirin(200 ppm in diet, everyday) or meloxicam(162 ppm in diet, everyday). Compare the tumor growth and survival after treatment between them. Results Each of aspirin and meloxicam treatment significantly suppressed the growth of OVCAR-3 tumors xenotransplanted subcutaneously as compared to control. The inhibition rate of OVCAR-3 tumor growth was higher in the meloxicam treatment group than in the aspirin treatment group( P<0.05). Meloxicam treatment significantly prolonged the survival of mice with malignant ascites derived from DISS cells as compared to control and aspirin treatment. There was no significant difference in survival between control and aspirin treatment. Conclusion These results indicated that a selective COX-2 inhibitor produced greater anti-tumor effect against ovarian cancer than a nonselective COX inhibitor and that meloxicam may have a potential of leading to a novel therapeutic strategy against ovarian cancer.
引文
[1]van de Laar R and LF Massuger.Pelvic inflammatory disease and ovarian cancer[J].Lancet Oncol,2011,12(13):1184;author reply 1184-1185.doi:10.1016/S1470-2045(11)70352-7
[2]Xin B,Y Yokoyama,T Shigeto,et al.Anti-tumor effect of non-steroidal anti-inflammatory drugs on human ovarian cancers[J].Pathol Oncol Res,2007,13(4):365-369.doi:PAOR.2007.13.4.0365
[3]Vital-Reyes V,C Rodriguez-Burford,DC Chhieng,et al.Celecoxib inhibits cellular growth,decreases Ki-67 expression and modifies apoptosis in ovarian cancer cell lines[J].Arch Med Res,2006,37(6):689-695.doi:10.1016/j.arcmed.2005.11.014
[4]Patel MM and AF Amin.Formulation and development of release modulated colon targeted system of meloxicam for potential application in the prophylaxis of colorectal cancer[J].Drug Deliv,2011,18(4):281-293.doi:10.3109/10717544.2010.538447
[5]Kim HJ,GW Yim,EJ Nam,et al.Synergistic Effect of COX-2 Inhibitor on Paclitaxel-Induced Apoptosis in the Human Ovarian Cancer Cell Line OVCAR-3[J].Cancer Res Treat,2014,46(1):81-92.doi:10.4143/crt.2014.46.1.81
[6]Cramer DW,BL Harlow,L Titus-Ernstoff,et al.Over-thecounter analgesics and risk of ovarian cancer[J].Lancet,1998,351(9096):104-107.doi:10.1016/S0140-6736(97)08064-1
[7]Gurpinar E,WE Grizzle and GA Piazza.COX-Independent Mechanisms of Cancer Chemoprevention by Anti-Inflammatory Drugs[J].Front Oncol,2013,3:181.doi:10.3389/fonc.2013.00181
[8]Harris RE,J Beebe and GA Alshafie.Reduction in cancer risk by selective and nonselective cyclooxygenase-2(COX-2)inhibitors[J].J Exp Pharmacol,2012,4:91-96.doi:10.2147/JEP.S23826
[9]Feng D,T Zhao,K Yan,et al.Gonadotropins promote human ovarian cancer cell migration and invasion via a cyclooxygenase 2-dependent pathway[J].Oncol Rep,2017,38(2):1091-1098.doi:10.3892/or.2017.5784
[10]Drake JG and JL Becker.Aspirin-induced inhibition of ovarian tumor cell growth[J].Obstet Gynecol,2002,100(4):677-682
[11]di Palma A,G Matarese,V Leone,et al.Aspirin reduces the outcome of anticancer therapy in Meth A-bearing mice through activation of AKT-glycogen synthase kinase signaling[J].Mol Cancer Ther,2006,5(5):1318-1324.doi:10.1158/1535-7163.MCT-05-0473
[12]Din FV,E Theodoratou,SM Farrington,et al.Effect of aspirin and NSAIDs on risk and survival from colorectal cancer[J].Gut,2010,59(12):1670-1679.doi:10.1136/gut.2009.203000
[13]Suri A,X Sheng,KM Schuler,et al.The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer[J].Oncotarget,2016,7(26):39582-39594.doi:10.18632/oncotarget.8659
[14]Beeghly-Fadiel A,Ramahi M E,Wilson A,et al.Abstract A63:The importance of cyclooxygenase 1 and 2 expression in ovarian cancer survival:Notable differences by histologic subtype.[J].Clin Cancer Res,2016,22(2 Supplement):A63-A63
[15]Trabert B,Ness R B,Lociganic W H,et al.Aspirin,nonaspirin nonsteroidal anti-inflammatory drug,and acetaminophen use and risk of invasive epithelial ovarian cancer:a pooled analysis in the Ovarian Cancer Association Consortium.[J].J Natl Cancer Inst,2014,106(2):djt431.
[2]Xin B,Y Yokoyama,T Shigeto,et al.Anti-tumor effect of non-steroidal anti-inflammatory drugs on human ovarian cancers[J].Pathol Oncol Res,2007,13(4):365-369.doi:PAOR.2007.13.4.0365
[3]Vital-Reyes V,C Rodriguez-Burford,DC Chhieng,et al.Celecoxib inhibits cellular growth,decreases Ki-67 expression and modifies apoptosis in ovarian cancer cell lines[J].Arch Med Res,2006,37(6):689-695.doi:10.1016/j.arcmed.2005.11.014
[4]Patel MM and AF Amin.Formulation and development of release modulated colon targeted system of meloxicam for potential application in the prophylaxis of colorectal cancer[J].Drug Deliv,2011,18(4):281-293.doi:10.3109/10717544.2010.538447
[5]Kim HJ,GW Yim,EJ Nam,et al.Synergistic Effect of COX-2 Inhibitor on Paclitaxel-Induced Apoptosis in the Human Ovarian Cancer Cell Line OVCAR-3[J].Cancer Res Treat,2014,46(1):81-92.doi:10.4143/crt.2014.46.1.81
[6]Cramer DW,BL Harlow,L Titus-Ernstoff,et al.Over-thecounter analgesics and risk of ovarian cancer[J].Lancet,1998,351(9096):104-107.doi:10.1016/S0140-6736(97)08064-1
[7]Gurpinar E,WE Grizzle and GA Piazza.COX-Independent Mechanisms of Cancer Chemoprevention by Anti-Inflammatory Drugs[J].Front Oncol,2013,3:181.doi:10.3389/fonc.2013.00181
[8]Harris RE,J Beebe and GA Alshafie.Reduction in cancer risk by selective and nonselective cyclooxygenase-2(COX-2)inhibitors[J].J Exp Pharmacol,2012,4:91-96.doi:10.2147/JEP.S23826
[9]Feng D,T Zhao,K Yan,et al.Gonadotropins promote human ovarian cancer cell migration and invasion via a cyclooxygenase 2-dependent pathway[J].Oncol Rep,2017,38(2):1091-1098.doi:10.3892/or.2017.5784
[10]Drake JG and JL Becker.Aspirin-induced inhibition of ovarian tumor cell growth[J].Obstet Gynecol,2002,100(4):677-682
[11]di Palma A,G Matarese,V Leone,et al.Aspirin reduces the outcome of anticancer therapy in Meth A-bearing mice through activation of AKT-glycogen synthase kinase signaling[J].Mol Cancer Ther,2006,5(5):1318-1324.doi:10.1158/1535-7163.MCT-05-0473
[12]Din FV,E Theodoratou,SM Farrington,et al.Effect of aspirin and NSAIDs on risk and survival from colorectal cancer[J].Gut,2010,59(12):1670-1679.doi:10.1136/gut.2009.203000
[13]Suri A,X Sheng,KM Schuler,et al.The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer[J].Oncotarget,2016,7(26):39582-39594.doi:10.18632/oncotarget.8659
[14]Beeghly-Fadiel A,Ramahi M E,Wilson A,et al.Abstract A63:The importance of cyclooxygenase 1 and 2 expression in ovarian cancer survival:Notable differences by histologic subtype.[J].Clin Cancer Res,2016,22(2 Supplement):A63-A63
[15]Trabert B,Ness R B,Lociganic W H,et al.Aspirin,nonaspirin nonsteroidal anti-inflammatory drug,and acetaminophen use and risk of invasive epithelial ovarian cancer:a pooled analysis in the Ovarian Cancer Association Consortium.[J].J Natl Cancer Inst,2014,106(2):djt431.