Archives of Toxicology, 2014, 88(3):625-35.

Genistein modulates the anti‑tumor activity of cisplatin in MCF‑7 breast and HT‑29 colon cancer cells

Xiao Juan Hu, Ming Yong Xie, Felix M. Kluxen, et al

Department of Cellular and Molecular Sports Medicine, Institute of Cardiovascular Research and Sports Medicine German Sports University Cologne Koeln Germany; State Key Laboratory of Food Science and Technology Nanchang University, Nanchang, China; Basic Medical College Nanchang University, Nanchang, China

The function of genistein (GEN) on tumor prevention and tumor promotion is discussed controversially. A possible interference of GEN with chemotherapy has been only rarely addressed so far. In this study, effects of GEN on the anti-tumor activity of cisplatin (CIS) were investigated in the presence and absence of estradiol (10(-10) M) in MCF-7 breast and HT-29 colon cancer cells. Cells were treated with graded concentrations of GEN (10(-4)-10(-6) M), E2, CIS and combinations. Cell growth, proliferation and apoptosis were determined as well as the expression level of PCNA, Ki67 and BCL-2 family members. CIS and GEN 10(-4) M inhibited cell growth and induced apoptosis in MCF-7 and HT-29 cells in the presence and absence of E2. Co-treatment with CIS and 10(-4)M GEN resulted in additive effects. In concentrations of 10(-5) and 10(-6) M, GEN stimulated cell growth in MCF-7 cells. It promoted proliferation, inhibited apoptosis and counteracted the anti-tumor activity of CIS in MCF-7 and HT-29 cells. Particularly the ability of CIS to induce apoptosis was antagonized. In ER alpha-positive MCF-7 cells, but not in ER alpha-negative HT-29 cells, E2 was able to neutralize the anti-CIS effects of GEN. Our data provide evidence that GEN in the absence of E2, a situation which occurs in postmenopausal women, directly affects the anti-tumor activity of cytostatic drugs like CIS. The exact molecular mechanism has to be investigated in future studies.

德国《毒理学档案》，2014年3月

在 MCF-7 乳腺癌和HT-29结肠癌细胞中金雀异黄素可以调节顺铂的抗肿瘤活性

胡晓娟，谢明勇，费利克斯  M 科伦克森，等

德国体育大学心血管研究和运动医学研究院细胞和分子运动医学系；中国南昌市南昌大学食品科学与技术国家重点实验室和基础医学院

金雀异黄素（GEN）对肿瘤预防和促进肿瘤的作用被争议性地讨论。GEN 与化疗的可能性干扰到目前为止已经很少被涉及。在此研究中，在存在和缺乏(10^-10 M)雌二醇的MCF-7 乳腺癌和结肠癌细胞 HT- 29 中探究了GEN对顺铂 （CIS） 抗肿瘤活性的影响。用梯度浓度的GEN(10^-4-10^-6 M)、 E2、 CIS和组合物处理细胞。细胞生长、 增殖、 凋亡以及增殖细胞核抗原、 Ki67 和 BCL-2 家族成分的表达水平被测定。CIS和 GEN 10^-4 M 抑制MCF-7 和 HT-29 细胞的生长并诱导细胞凋亡在E2存在和缺乏的情况下。CIS和 10^-4 M GEN的联合治疗导致叠加的作用。在浓度为 10^-5 和 10^-6 M时，GEN刺激MCF-7 细胞的生长。它促进了细胞增殖、 抑制了细胞凋亡并消除了CIS对 MCF-7 和 HT-29 细胞的抗肿瘤活性。特别是CIS诱导细胞凋亡的能力被阻抗。在 ERα-阳性 MCF-7 细胞，而不是在 ERα-阴性HT-29 细胞中，E2 能够抵消GEN的抗CIS作用。我们的数据表明在E2缺乏的情况下，在绝经后的妇女发生的这种情况下，GEN直接影响到像CIS这样细胞抑制剂的抗肿瘤活性。确切的分子机制需要在未来的研究中探究。