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地西他滨增强卡培他滨在小鼠 B16 黑色素瘤异体移植瘤和人非小细胞肺癌 A549 异种移植瘤中的抗肿瘤作用。

DCA increases the antitumor effects of capecitabine in a mouse B16 melanoma allograft and a human non-small cell lung cancer A549 xenograft.

机构信息

Department of Biochemistry, School of Life Science, Fudan University, Handan Road 220, Shanghai, 200433, China.

出版信息

Cancer Chemother Pharmacol. 2013 Nov;72(5):1031-41. doi: 10.1007/s00280-013-2281-z. Epub 2013 Sep 17.

DOI:10.1007/s00280-013-2281-z
PMID:24043136
Abstract

PURPOSE

Capecitabine is one of the few chemotherapy drugs with high oral availability. Recently, sodium dichloroacetate (DCA) has shown great potential as an anticancer agent. In the present study, we assessed the anticancer effect of DCA in combination with capecitabine for cancers that modestly expressed TP.

METHODS

A mouse B16 melanoma allograft and a human non-small cell lung cancer A549 xenograft were used to assess the effect of DCA and capecitabine combined treatment. Histology and immunohistochemistry were used to detect the apoptosis and proliferation of cancer cells. Real-time PCR and Western blot were carried out to detect the expression of TP and caspases, respectively.

RESULTS

For the first time, we report that DCA increased the antitumor effects of capecitabine in a mouse B16 allograft and a human A549 xenograft by promoting apoptosis of tumor cells. DCA has little effect on the expression of TP.

CONCLUSIONS

Our finding suggests that DCA in combination with capecitabine might be potential as a new therapeutic regimen against some cancers.

摘要

目的

卡培他滨是少数口服生物利用度高的化疗药物之一。最近,二氯乙酸钠(DCA)作为一种抗癌药物显示出巨大的潜力。本研究评估了 DCA 联合卡培他滨治疗低表达 TP 的癌症的抗癌效果。

方法

使用小鼠 B16 黑色素瘤移植瘤和人非小细胞肺癌 A549 异种移植瘤来评估 DCA 和卡培他滨联合治疗的效果。组织学和免疫组织化学用于检测癌细胞的凋亡和增殖。实时 PCR 和 Western blot 分别用于检测 TP 和半胱天冬酶的表达。

结果

我们首次报道,DCA 通过促进肿瘤细胞凋亡,增加了卡培他滨在小鼠 B16 移植瘤和人 A549 异种移植瘤中的抗肿瘤作用。DCA 对 TP 的表达影响不大。

结论

我们的发现表明,DCA 联合卡培他滨可能是治疗某些癌症的一种新的治疗方案。

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