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三七增强5-氟尿嘧啶对人结肠癌细胞的抗癌作用。

Notoginseng enhances anti-cancer effect of 5-fluorouracil on human colorectal cancer cells.

作者信息

Wang Chong-Zhi, Luo Xiaoji, Zhang Bin, Song Wen-Xin, Ni Ming, Mehendale Sangeeta, Xie Jing-Tian, Aung Han H, He Tong-Chuan, Yuan Chun-Su

机构信息

Tang Center for Herbal Medicine Research, The University of Chicago, Chicago, IL 60637, USA.

出版信息

Cancer Chemother Pharmacol. 2007 Jun;60(1):69-79. doi: 10.1007/s00280-006-0350-2. Epub 2006 Sep 29.

Abstract

PURPOSE

Panax notoginseng is a commonly used Chinese herb. Although a few studies have found that notoginseng shows anti-tumor effects, the effect of this herb on colorectal cancer cells has not been investigated. 5-Fluorouracil (5-FU) is a chemotherapeutic agent for the treatment of colorectal cancer that interferes with the growth of cancer cells. However, this compound has serious side effects at high doses. In this study, using HCT-116 human colorectal cancer cell line, we investigated the possible synergistic anti-cancer effects between notoginseng flower extract (NGF) and 5-FU on colon cancer cells.

METHODS

The anti-proliferation activity of these modes of treatment was evaluated by MTS cell proliferation assay. Apoptotic effects were analyzed by using Hoechst 33258 staining and Annexin-V/PI staining assays. The anti-proliferation effects of four major single compounds from NGF, ginsenosides Rb1, Rb3, Rc and Rg3 were also analyzed.

RESULTS

Both 5-FU and NGF inhibited proliferation of HCT-116 cells. With increasing doses of 5-FU, the anti-proliferation effect was slowly increased. The combined usage of 5-FU 5 microM and NGF 0.25 mg/ml, significantly increased the anti-proliferation effect (59.4 +/- 3.3%) compared with using the two medicines separately (5-FU 5 microM, 31.1 +/- 0.4%; NGF 0.25 mg/ml, 25.3 +/- 3.6%). Apoptotic analysis showed that at this concentration, 5-FU did not exert an apoptotic effect, while apoptotic cells induced by NGF were observed, suggesting that the anti-proliferation target(s) of NGF may be different from that of 5-FU, which is known to inhibit thymidilate synthase.

CONCLUSIONS

This study demonstrates that NGF can enhance the anti-proliferation effect of 5-FU on HCT-116 human colorectal cancer cells and may decrease the dosage of 5-FU needed for colorectal cancer treatment.

摘要

目的

三七是一种常用的中药材。尽管一些研究发现三七具有抗肿瘤作用,但该药材对结肠癌细胞的作用尚未得到研究。5-氟尿嘧啶(5-FU)是一种用于治疗结肠癌的化疗药物,可干扰癌细胞的生长。然而,该化合物在高剂量时有严重的副作用。在本研究中,我们使用HCT-116人结肠癌细胞系,研究了三七花提取物(NGF)与5-FU对结肠癌细胞可能的协同抗癌作用。

方法

通过MTS细胞增殖试验评估这些治疗方式的抗增殖活性。使用Hoechst 33258染色和膜联蛋白-V/碘化丙啶染色试验分析凋亡效应。还分析了NGF中四种主要单一化合物人参皂苷Rb1、Rb3、Rc和Rg3的抗增殖作用。

结果

5-FU和NGF均抑制HCT-116细胞的增殖。随着5-FU剂量的增加,抗增殖作用缓慢增强。与单独使用两种药物相比(5-FU 5 microM,31.1 +/- 0.4%;NGF 0.25 mg/ml,25.3 +/- 3.6%),联合使用5 microM的5-FU和0.25 mg/ml的NGF可显著增强抗增殖作用(59.4 +/- 3.3%)。凋亡分析表明,在此浓度下,5-FU未发挥凋亡作用,而观察到NGF诱导的凋亡细胞,这表明NGF的抗增殖靶点可能与已知抑制胸苷酸合成酶的5-FU不同。

结论

本研究表明,NGF可增强5-FU对HCT-116人结肠癌细胞的抗增殖作用,并可能降低结肠癌治疗所需的5-FU剂量。

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