前列腺癌是男性常见的恶性肿瘤之一，大多数晚期前列腺癌患者最初对雄激素剥夺疗法疗效较好，然而几乎所有患者最终会对该疗法产生抗性而失效。以多烯紫杉醇（Docetaxel）为基础的化疗作为当前去势难治性前列腺癌(Castration resistant prostate cancer, CRPC)最有效的治疗选择，相关研究表明其在提高总体生存率上仍存在困难。
中国科学院成都生物研究所唐亚雄博士在美国加州大学尔湾分校Zi课题组访问期间，利用番茄红素（Lycopene）具有抗前列腺癌活性的特点，率先在体内体外开展了番茄红素与多烯紫杉醇联用在前列腺癌中的抗癌分子机制研究。研究表明，Lycopene对前列腺癌细胞的生长抑制效果与胰岛素样生长因子I受体IGF-IR水平呈正相关；而且Lycopene对IGF-IR较高表达的DU145细胞更有效地提高了Docetaxel的生长抑制效应；在DU145裸鼠皮下异种移植瘤模型中，Lycopene与Docetaxel联用比单独使用Docetaxel能提高38%的抗瘤疗效(P=.047)；从分子机制来看，首次揭示了Lycopene可通过抑制IGF-I的刺激以及增加IGF-BP3的分泌表达从而抑制IGF-IR活性，而且也能抑制下游的Akt激酶活性和Survivin的表达从而导致细胞凋亡。
上述研究揭示了Lycopene与Docetaxel的组合在胰岛素样生长因子I受体较高表达的去势难治性前列腺癌治疗中的临床意义。该研究结果为前列腺癌的预防与临床治疗奠定了物质基础与分子机制。相关论文发表在NEOPLASIA上。（生物谷Bioon.com）
生物谷推荐原文出处：
Neoplasia 2011,13(2):108-119
Lycopene enhances docetaxel’s effect in castration-resistant prostate cancer associated with insulin-like growth factor I receptor levels
Yaxiong Tang, Basmina Parmakhtiar, Anne R. Simoneau, Jun Xie, John Fruehauf, Micheal Lilly and Xiaolin Zi
Docetaxel is currently the most effective drug for treatment of castration-resistant prostate cancer (CRPC), but only extends life by an average of two months. Lycopene, an antioxidant phytochemical, has antitumor activity against prostate cancer (PCa) in several models, and is generally safe. We present data on the interaction between docetaxel and lycopene in CRPC models. The growth inhibitory effect of lycopene on PCa cell lines was positively associated with IGF-IR levels. Additionally, lycopene treatment enhanced the growth inhibitory effect of docetaxel more effectively on DU145 cells with IGF-IR high expression than on those PCa cell lines with IGF-IR low expression. In a DU145 xenograft tumor model, docetaxel plus lycopene caused tumor regression, with a 38% increase in anti-tumor efficacy (P=0.047) when compared to docetaxel alone. Lycopene inhibited IGF-IR activation via inhibiting IGF-I stimulation and by increasing the expression and secretion of IGFBP-3. Downstream effects include inhibition of AKT kinase activity and survivin expression, followed by apoptosis. Together, the enhancement of docetaxel?s antitumor efficacy by lycopene supplementation justifies further clinical investigation of lycopene and docetaxel combination for CRPC patients. CRPC patients with IGF-IR overexpressing tumors may be most likely to benefit from this combination.
