5-Fluorouracil combined with apigenin enhances anticancer activity through induction of apoptosis in human breast cancer MDA-MB-453 cells
5-Fluorouracil combined with apigenin enhances anticancer activity through induction of apoptosis in human breast cancer MDA-MB-453 cells
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DOI：
10.3892/or_00000598
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发表时间：
2009-12-01
期刊：
影响因子：
4.2
通讯作者：
Kim, Gun-Hee
中科院分区：
文献类型：
--
作者：
Choi, Eun Jeong;Kim, Gun-Hee
我们研究了5-氟尿嘧啶和芹菜素联合处理对人乳腺癌MDA-MB-453细胞增殖和凋亡的影响及其机制。MDA-MB-453细胞已被证明过表达ErbB 2，对5-氟尿嘧啶具有耐药性; 5-氟尿嘧啶显示出小的剂量依赖性抗增殖作用，所有IC（50）均为90 μ M。有趣的是，与芹菜素的组合处理显著降低了抗性。与单独暴露于5-氟尿嘧啶的细胞增殖相比，暴露于IC（50）和芹菜素（5，10，50和100 μ M）的5-氟尿嘧啶的细胞增殖被显著抑制。这种抑制反过来导致凋亡，如凋亡细胞数量增加和半胱天冬酶-3活化所证明的。为了研究5-氟尿嘧啶和芹菜素的组合诱导细胞凋亡的机制，分析了ErbB 2的表达。ErbB 2的水平是不变的5-氟尿嘧啶单独，但在5-氟尿嘧啶加芹菜素处理的细胞急剧减少。此外，与单独的5-氟尿嘧啶相比，浓度>10 μ M的5-氟尿嘧啶与芹菜素组合通过抑制Akt表达而产生促凋亡作用。综上所述，我们的研究结果表明，5-氟尿嘧啶与芹菜素协同作用，通过下调ErbB 2表达和Akt信号转导抑制细胞生长并诱导细胞凋亡。
We investigated the effects of combined treatment with 5-fluorouracil and apigenin on proliferation and apoptosis, as well as the underlying mechanism, in human breast cancer MDA-MB-453 cells. The MDA-MB-453 cells, which have been shown to overexpress ErbB2, were resistant to 5-fluorouracil; 5-fluorouracil exhibited a small dose-dependent anti-proliferative effect, with all IC(50) of 90 mu M. Interestingly, combined treatment with apigenin significantly decreased the resistance. Cellular proliferation was significantly inhibited in cells exposed to 5-fluorouracil at its IC(50) and apigenin (5, 10, 50 and 100 mu M), compared with proliferation in cells exposed to 5-fluorouracil alone. This inhibition in turn led to apoptosis, as evidenced by an increased number of apoptotic cells and the activation of caspase-3. To investigate the mechanism by which the combination of 5-fluorouracil and apigenin induces apoptosis, ErbB2 expression was analyzed. The level of ErbB2 was unchanged by 5-fluorouracil alone but was drastically reduced in cells treated with 5-fluorouracil plus apigenin. Moreover, compared with 5-fluorouracil alone, 5-fluorouracil in combination with apigenin at concentrations >10 mu M exerted a pro-apoptotic effect via the inhibition of Akt expression. Taken together, our results Suggest that 5-fluorouracil acts synergistically with apigenin inhibiting cell growth and inducing apoptosis via the down-regulation of ErbB2 expression and Akt signaling.