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与环加氧酶(COX)抑制剂联合使用对人卵巢癌细胞株SKOV-3植入小鼠的卵巢癌生长抑制作用是否比单独使用紫杉醇更好。每天两次分别用100 mg / kg celecoxib(一种COX-2选择性抑制剂)或与3 mg / kg SC-560(一种COX-1选择性抑制剂)联合饲喂动物,分别用20 mg / kg紫杉醇治疗。每周一次腹膜内(IP)或与celecoxib或SC-560 / celecoxib /紫杉醇联合使用3周。为了测试联合治疗的机制,通过免疫组织化学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),并用末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸来检测凋亡细胞的指数。缺口标记(TUNEL)方法。第14天时,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,细胞周期cyclin D1阳性细胞的增殖指数和凋亡指数分别为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)。在SC-560 / celecoxib /紫杉醇(39.57 /-4.98)和对照组(73.2 /-1.96)组之间观察到MVD的统计显着性(p <0.001)。我们的研究结果表明,紫杉醇和COX抑制剂的联合抗肿瘤药效可能优于单独使用紫杉醇作为抗小鼠卵巢癌的药物疗法,并且联合治疗的协同作用可能部分通过加速凋亡以及抑制细胞增殖和血管生成来介导。 。

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