Meng Cuicui, Lu Zhonghua, Fang Mingming, Zhou Xifa, Dai Kejun, Zhang Shuyu, Luo Judong, Luo Zhibin
Department of Radiotherapy, Changzhou Cancer Hospital, Soochow University Changzhou 213001, China.
School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Soochow University Suzhou 215123, China.
Int J Clin Exp Pathol. 2014 Oct 15;7(11):7622-32. eCollection 2014.
Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has been reported to have antitumor effects. In some tumor models, the combination of celecoxib with chemotherapy agents has shown synergistic antitumor effect; however, the effect of celecoxib combination with tegafur/gimeracil/oteracil potassium on the malignant biological behaviors of gastric cancer in nude mice is unclear. In this study, female nude mice were subcutaneously transplanted with SGC-7901 gastric cancer cells. When the tumor model formed, the mice were divided into control group, celecoxib group, tegafur/gimeracil/oteracil potassium group, and the combination of both drug regimens group. Mice were treated for 3 weeks. Following treatment, the proliferating index was calculated, apoptosis related proteins, COX-2, vascular endothelial growth factor-C (VEGF-C) and lymphatic vessel density were quantified in tumor tissues by immunohistochemistry. Apoptosis was evaluated by TUNEL staining. The results revealed that celecoxib and tegafur/gimeracil/oteracil potassium alone significantly inhibited tumor growth. The combination of these two drugs showed a synergistic antitumor effect. Both celecoxib and tegafur/gimeracil/oteracil potassium alone inhibited proliferation and promoted apoptosis. The combination of these two drugs further enhanced this anticancer effect. Both celecoxib and the combination treatment inhibited lymphangiogenesis and the expression of COX-2 and VEGF-C. However, tegafur/gimeracil/oteracil potassium treatment had no obvious effect on lymphangiogenesis. These results suggested that the combination of celecoxib and tegafur/gimeracil/oteracil potassium produced a synergistic antitumor effect, possibly by inhibiting the proliferation of tumor cells and promoting apoptosis. Celecoxib and celecoxib in combination with tegafur/gimeracil/oteracil potassium possibly by reducing the expression of COX-2, in turn down-regulating the expression of VEGF-C, resulted in the inhibition of lymphangiogenesis.
塞来昔布是一种选择性环氧化酶-2（COX-2）抑制剂，据报道具有抗肿瘤作用。在一些肿瘤模型中，塞来昔布与化疗药物联合使用已显示出协同抗肿瘤作用；然而，塞来昔布与替吉奥联合使用对裸鼠胃癌恶性生物学行为的影响尚不清楚。在本研究中，将雌性裸鼠皮下移植SGC-7901胃癌细胞。当肿瘤模型形成后，将小鼠分为对照组、塞来昔布组、替吉奥组以及两种药物联合组。小鼠接受治疗3周。治疗后，计算增殖指数，通过免疫组织化学对肿瘤组织中的凋亡相关蛋白、COX-2、血管内皮生长因子-C（VEGF-C）和淋巴管密度进行定量分析。通过TUNEL染色评估细胞凋亡情况。结果显示，单独使用塞来昔布和替吉奥均能显著抑制肿瘤生长。这两种药物联合使用表现出协同抗肿瘤作用。单独使用塞来昔布和替吉奥均能抑制增殖并促进细胞凋亡。这两种药物联合使用进一步增强了这种抗癌作用。塞来昔布及联合治疗均能抑制淋巴管生成以及COX-2和VEGF-C的表达。然而，替吉奥治疗对淋巴管生成没有明显影响。这些结果表明，塞来昔布与替吉奥联合使用产生协同抗肿瘤作用，可能是通过抑制肿瘤细胞增殖和促进细胞凋亡实现的。塞来昔布以及塞来昔布与替吉奥联合使用可能是通过降低COX-2的表达，进而下调VEGF-C的表达，从而抑制淋巴管生成。
