A COX-2 inhibitor enhances the antitumor effects of chemotherapy and radiotherapy for esophageal squamous cell carcinoma.
A COX-2 inhibitor enhances the antitumor effects of chemotherapy and radiotherapy for esophageal squamous cell carcinoma.
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DOI：
10.3892/ijo.2014.2300
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发表时间：
2014-04
影响因子：
5.2
通讯作者：
Gulbostan Yusup;Y. Akutsu;Muradil Mutallip;W. Qin;Xin Hu;Aki Komatsu-Akimoto;Isamu Hoshino;N. Hanari;M. Mori;Naoki Akanuma;Y. Isozaki;H. Matsubara
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文献类型：
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作者：
Gulbostan Yusup;Y. Akutsu;Muradil Mutallip;W. Qin;Xin Hu;Aki Komatsu-Akimoto;Isamu Hoshino;N. Hanari;M. Mori;Naoki Akanuma;Y. Isozaki;H. Matsubara
环加氧酶-2 (COX-2) 是前列腺素 (PG) 合成的关键酶，已被证明在多种类型的癌症中过度表达。 COX-2 在肿瘤进展中的功能最近已被阐明。在 COX-2 过度表达的肿瘤中，抗肿瘤作用受到抑制。我们研究了塞来昔布（一种 COX-2 抑制剂）通过降低 COX-2 活性来增强食管鳞状细胞癌 (ESCC) 化疗和放疗的抗肿瘤作用。我们使用塞来昔布和 5-FU/放射处理的人食管鳞状细胞系 TE2 和 T.Tn，然后进行细胞活力测定。还测量了二氢嘧啶脱氢酶（DPD）、乳清酸磷酸核糖转移酶（OPRT）mRNA和PGE2表达的变化。此外，还评估了塞来昔布和5-FU处理的细胞的凋亡变化以及侵袭和迁移活性。实验表明，5-FU/辐射和COX-2抑制剂的组合强烈抑制T.Tn和TE2增殖。抑制 COX-2 活性会导致 TE2/T.Tn 细胞中 PGE2 水平降低。用COX-2抑制剂和5-FU处理后，耐药细胞中OPRT表达上调，DPD表达下调。此外，COX-2抑制剂和5-FU联合治疗显着抑制了细胞侵袭和迁移活性。因此，COX-2抑制剂可作为ESCC抗肿瘤药物和放射治疗的有效增强剂。
Cyclooxygenase-2 (COX-2) is a key enzyme of prostaglandin (PG) synthesis that has been demonstrated to be overexpressed in several types of cancers. The function of COX-2 in tumor progression has been recently elucidated. In tumors in which COX-2 is overexpressed, the antitumor effects are suppressed. We examined the effects of celecoxib, a COX-2 inhibitor, in enhancing the antitumor effects of chemotherapy and radiotherapy for esophageal squamous cell carcinoma (ESCC) by reducing the COX-2 activity. We used the human esophageal squamous cell lines TE2 and T.Tn treated with celecoxib and 5-FU/radiation, after which cell viability assays were performed. Changes in the expressions of dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT) mRNA and PGE2 were also measured. In addition, apoptotic changes, and the invasion and migration activity in both the celecoxib and 5-FU treated cells were evaluated. The experiments showed that T.Tn and TE2 proliferation was strongly inhibited by the combination of 5-FU/radiation and the COX-2 inhibitor. Inhibiting the COX-2 activity induced a reduction in PGE2 levels in TE2/T.Tn cells. Following treatment with the COX-2 inhibitor and 5-FU, the OPRT expression was upregulated and the DPD expression was downregulated in the resistant cells. In addition, the combination treatment with the COX-2 inhibitor and 5-FU markedly inhibited both the cell invasion and migration activity. Therefore, COX-2 inhibitors can be useful enhancers of antitumor drugs and radiotherapy for ESCC.