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COX-2抑制剂的抗癌作用及其与胃癌血管生成和侵袭的相关性

Anti-cancer effects of COX-2 inhibitors and their correlation with angiogenesis and invasion in gastric cancer.

作者信息

Fu Suo-Lin, Wu Yun-Lin, Zhang Yong-Ping, Qiao Min-Min, Chen Ying

机构信息

Department of Gastroenterology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.

出版信息

World J Gastroenterol. 2004 Jul 1;10(13):1971-4. doi: 10.3748/wjg.v10.i13.1971.

Abstract

AIM

To observe the anti-cancer effects of COX-2 inhibitors and investigate the relationship between COX-2 inhibitors and angiogenesis, infiltration or metastasis in SGC7901 cancer xenografts.

METHODS

Thirty athymic mice xenograft models with human stomach cancer cell SGC7901 were established and divided randomly into 3 groups of 10 each. Sulindac, one non-specific COX inhibitor belonging to non-steroidal anti-inflammatory drugs (a series of COX inhibitors known as NSAIDs) and celecoxib, one selective COX-2 inhibitor (known as SCIs) were orally administered to mice of treatment groups. Immunohistochemistry was used to examine the expression of PCNA, CD44v6 and microvessel density (MVD). Apoptosis was detected by using TUNEL assay.

RESULTS

Tumors in sulindac and celecoxib groups were significantly smaller than those in control group from the second week after drug administration (P<0.01). In treatment group, the cell proliferation index was lower (P<0.05) and apoptosis index was higher (P<0.05) than those in control groups. Compared with the controls, microvessel density was reduced (P<0.01) and expression of CD44v6 on tumor cells was weakened (P<0.05) in treatment groups.

CONCLUSION

COX-2 inhibitors have anticancer effects on gastric cancer. They play important roles in angiogenesis and infiltration or metastasis of stomach carcinoma. The anticancer effects of COX-2 inhibitors may include inducing apoptosis, suppressing proliferation, reducing angiogenesis and weakening invasiveness.

摘要

目的

观察COX-2抑制剂的抗癌作用,并研究COX-2抑制剂与SGC7901癌异种移植瘤血管生成、浸润或转移之间的关系。

方法

建立30只人胃癌细胞SGC7901的裸鼠异种移植模型,并随机分为3组,每组10只。给治疗组小鼠口服舒林酸(一种属于非甾体抗炎药的非特异性COX抑制剂,即一系列被称为NSAIDs的COX抑制剂)和塞来昔布(一种选择性COX-2抑制剂,即所谓的SCIs)。采用免疫组织化学法检测PCNA、CD44v6的表达及微血管密度(MVD)。用TUNEL法检测细胞凋亡。

结果

给药后第2周起,舒林酸组和塞来昔布组的肿瘤明显小于对照组(P<0.01)。治疗组的细胞增殖指数低于对照组(P<0.05),凋亡指数高于对照组(P<0.05)。与对照组相比,治疗组的微血管密度降低(P<0.01),肿瘤细胞上CD44v6的表达减弱(P<0.05)。

结论

COX-2抑制剂对胃癌有抗癌作用。它们在胃癌的血管生成、浸润或转移中起重要作用。COX-2抑制剂的抗癌作用可能包括诱导细胞凋亡、抑制增殖、减少血管生成和减弱侵袭性。

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