Wang Hong-jing, Peng Zhi-lan, Liu Xiao-qing, Yang Kai-xuan, Lou Jiang-yan, Luo Feng-ming
Department of Pathology, West China Second Hospital, Sichuan University, Chengdu 610041, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2007 Jun;38(3):428-32.
To evaluate the effects of two commonly used non-steroidal anti-inflammatory drugs (NSAIDs) Celecoxib and Aspirin on the SKOV3 cell growth, apoptosis and neoplasm genesis of ovarian cancer in vitro and vivo.
The proliferation of SKOV3 cells were determined by MTT assay, the apoptosis of cell were measured by flow cytometry (FCM), and the cell morphologic changes were observed under inverted phase contrast microscope. Xenografted nude mice models of human ovarian cancer were established, and then randomly allocated to treatment or control group, which was administered with either Celecoxib at the dosage of 10, 25, 50 mg/kg or distilled water alone (control) orally daily for 56 d. The mice weight, tumor volume and drug side effects were detected.
A dose-dependent inhibition of proliferation of SKOV3 cell appeared after Celecoxib or Aspirin administered for 24 h, and Celecoxib had more inhibiting efficiency to cell growth than Aspirin did. The inhibitory concentration 50% (IC50) in this assay for Celecoxib was 5X 10(-5) mol/L,whereas for Aspirin was 7X 10(-3) mol/L. With cell morphology the "vacuole" presented in the cytoplasm. In contrast to the control, the apoptotic rates (47. 1% and 15. 7%) of SKOV3 were increased after treatment with Celecoxib (5 X 10(-5) mol/L) and Aspirin(7 X 10(-3) mol/L). In nude mice, the average volume of tumor from control mice was (3. 283+/- 0. 432) cm(3) as compared with (2. 457+/- 0. 224) cm(3), (2. 198+/- 0. 500) cm(3), (2. 017+/-0. 166) cm' from Celecoxib mice (10, 25, 50 mg/kg), P<0. 05, and the rates of tumor growth inhibited by 3 Celecoxib dosages to SKOV3 cell burden mice were 25. 20%, 33. 00% and 38. 60%, in a dose-and time-dependent manner, and histopathologic examinations of kidney, liver, stomach and bowel showed no abnormality, with implying no untoward side effects.
Both COX-2 specific inhibitor Celecoxib and non-selective inhibitor Aspirin can potentially inhibit the tumor growth and induce apoptosis of SKOV3 cells, and the effect of Celecoxib is more potential than that of Aspirin.
评估两种常用非甾体抗炎药塞来昔布和阿司匹林对卵巢癌SKOV3细胞体外及体内生长、凋亡和肿瘤发生的影响。
采用MTT法检测SKOV3细胞增殖,流式细胞术(FCM)检测细胞凋亡,倒置相差显微镜观察细胞形态变化。建立人卵巢癌裸鼠移植瘤模型,随机分为治疗组和对照组,治疗组分别给予10、25、50mg/kg塞来昔布或蒸馏水(对照),每日经口给药,共56天。检测小鼠体重、肿瘤体积及药物副作用。
塞来昔布或阿司匹林作用24小时后,SKOV3细胞增殖呈剂量依赖性抑制,且塞来昔布对细胞生长的抑制作用强于阿司匹林。本实验中塞来昔布的半数抑制浓度(IC50)为5×10⁻⁵mol/L,而阿司匹林为7×10⁻³mol/L。细胞形态上,细胞质中出现“空泡”。与对照组相比,用塞来昔布(5×10⁻⁵mol/L)和阿司匹林(7×10⁻³mol/L)处理后,SKOV3细胞的凋亡率增加(分别为47.1%和15.7%)。在裸鼠中,对照组小鼠肿瘤平均体积为(3.283±0.432)cm³,而塞来昔布组(10、25、50mg/kg)小鼠肿瘤平均体积分别为(2.457±0.224)cm³、(2.198±0.500)cm³、(2.017±0.166)cm³,P<0.05,3种剂量塞来昔布对SKOV3细胞负荷小鼠肿瘤生长的抑制率分别为25.20%、33.00%和38.60%,呈剂量和时间依赖性,肾、肝、胃和肠的组织病理学检查未见异常,提示无不良副作用。
COX-2特异性抑制剂塞来昔布和非选择性抑制剂阿司匹林均能潜在抑制SKOV3细胞肿瘤生长并诱导其凋亡,且塞来昔布的作用更显著。