The present study was designed to investigate whether taxol in combination with cyclooxygenase (COX) inhibitors could be superior on inhibitory effect of ovarian cancer growth than taxol alone as drug therapy of mice implanted with human ovarian carcinoma cell line SKOV-3. The animals were treated with 100 mg/ kg celecoxib (a COX-2 selective inhibitor) alone or in combination with 3 mg/kg SC-560 (a COX-1 selective inhibitor) by gavage twice a day, 20mg/kg taxol alone by intraperitoneal (IP) once a week or in combination with celecoxib, or SC-560/celecoxib/taxol for 3 weeks. To test the mechanism of the combination treatment, the index of cell proliferation, expression of cyclin D1, and microvessel density (MVD) in tumor tissues were determined by immunohistochemistry and the index of apoptotic cells by the terminal-deoxynucleotidyl-transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) method. Mean tumor volume in the SC-560/celecoxib/taxol group was first significantly lower than control at day 14 (p < 0.05). In the SC-560/celecoxib/taxol group, the index of cell proliferation and apoptosis and quantification of cyclin D1-postive cells were 6.93%, 69.62%, and 19.14%, respectively, which are statistically significant compared with those of the control group (29.85%, p < 0.001; 32.81% and 36.99%, both p < 0.05). Statistical significance on MVD was observed between the SC-560/celecoxib/taxol (39.57 +/- 4.98) and the control (73.2 +/- 1.96) group (p < 0.001). Our results suggest that the combined antitumor efficacy of taxol and COX inhibitors may be superior to taxol alone as drug therapy against ovarian cancer in mice, and that synergism of the combination treatment in part may be mediated through accelerated apoptosis and suppression of cell proliferation and angiogenesis.

译文

本研究旨在研究紫杉醇联合环氧合酶 (COX) 抑制剂对卵巢癌生长的抑制作用是否优于单独使用紫杉醇作为植入人卵巢癌细胞系SKOV-3的小鼠的药物治疗。分别用100 mg/kg塞来昔布 (一种COX-2选择性抑制剂) 单独或与3 mg/kg SC-560 (一种COX-1选择性抑制剂) 联合每天两次灌胃,单独用20mg/kg紫杉醇腹腔 (IP) 每周一次或与塞来昔布联合治疗,或SC-560/塞来昔布/紫杉醇3周。为了测试联合治疗的机制,采用免疫组织化学方法测定肿瘤组织中细胞增殖指数,细胞周期蛋白D1的表达和微血管密度 (MVD),并通过末端脱氧核苷酸-转移酶介导的三磷酸脱氧尿苷缺口末端标记 (TUNEL) 方法测定凋亡细胞的指数。在第14天,SC-560/塞来昔布/紫杉醇组的平均肿瘤体积首先显着低于对照组 (p <0.05)。在SC-560/塞来昔布/紫杉醇组中,细胞增殖和凋亡指数以及细胞周期蛋白D1-postive的定量分别为6.93% 、69.62% 和19.14%,与对照组相比有统计学意义 (29.85%,p <0.001; 32.81% 和36.99%,均p <0.05)。SC-560/塞来昔布/紫杉醇 (39.57 +/- 4.98) 和对照组 (73.2 +/- 1.96) 之间的MVD有统计学意义 (p <0.001)。我们的结果表明,紫杉醇和COX抑制剂的联合抗肿瘤疗效可能优于单独的紫杉醇作为小鼠卵巢癌的药物治疗,并且联合治疗的协同作用部分可能通过加速凋亡和抑制细胞增殖和血管生成来介导。

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