Effects of capecitabine and vinorelbine on cell proliferation, metabolism and COX2 and p16 expression in breast cancer cell lines and solid tumour tissues

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• 作者：Wings T.Y. Loo ; H. Sasano ; Louis W.C. Chow
• 关键词：Capecitabine ; Vinorelbine ; Metastatic-breast-tumor ; p16 ; COX2
• 刊名：Biomedicine and Pharmacotherapy
• 出版年：2007
• 期刊代码：36_07533322
• 类别：med
• 出版时间：October 2007
• 卷：61
• 期：9
• 页码：596-600
• 文件大小：749 K

摘要

Capecitabine is a recently developed oral antineoplastic prodrug of 5-fluorouracil. It has demonstrated a favorable tolerability profile, with low incidence of myelosuppression. Vinorelbine, a third generation vinca alkaloid, works by inhibiting mitosis and interfering with cells’ ability to synthesize DNA and RNA. The present study investigates the therapeutic value of single use capecitabine on solid tumour tissues in vitro using breast cancer cell lines and as reference. The data is to be compared with the use of vinorelbine which is a conventionally applied drug for advanced breast cancer patients.

Methods

The trucut biopsies of 35 metastatic breast tumour patients were obtained. The tissues were cultured for 24 h. Capecitabine and vinorelbine were added according to the corresponding groups to be cultured by another 24 h. Plain medium was added for control group. The two cell lines chosen were BT-783 and MB-MDA-231 to act as a reference group. The metabolic rate of the tissues and cell lines were measured by ATP bioluminescence assay and the proliferation rate was measured by WST-1. The level of COX2 and p16 after capecitabine and vinorelbine treatment was assessed with immunohistochemical methods.

Results

One-way ANOVA revealed lower metabolic rate in test groups than control in cell lines and tumour tissues. WST-1 showed similar trend in both cell lines. COX2 and p16 staining showed decreases in cell size and number after drug use.

Conclusions

Capecitabine demonstrated similar inhibitory effects as vinorelbine in breast cancer cell lines and solid tumour tissues at decreasing cell proliferation and metabolism as well as decreasing the expression of metabolic proteins and tumor suppressor genes. Capecitabine also has the added benefits of convenient oral administration and lower cost.