前列腺癌是男性常見的惡性腫瘤之一,，大多數(shù)晚期前列腺癌患者最初對(duì)雄激素剝奪療法療效較好，然而幾乎所有患者最終會(huì)對(duì)該療法產(chǎn)生抗性而失效,。以多烯紫杉醇（Docetaxel）為基礎(chǔ)的化療作為當(dāng)前去勢(shì)難治性前列腺癌(Castration resistant prostate cancer, CRPC)最有效的治療選擇,，相關(guān)研究表明其在提高總體生存率上仍存在困難。
中國(guó)科學(xué)院成都生物研究所唐亞雄博士在美國(guó)加州大學(xué)爾灣分校Zi課題組訪問期間,，利用番茄紅素（Lycopene）具有抗前列腺癌活性的特點(diǎn),，率先在體內(nèi)體外開展了番茄紅素與多烯紫杉醇聯(lián)用在前列腺癌中的抗癌分子機(jī)制研究。研究表明,，Lycopene對(duì)前列腺癌細(xì)胞的生長(zhǎng)抑制效果與胰島素樣生長(zhǎng)因子I受體IGF-IR水平呈正相關(guān),；而且Lycopene對(duì)IGF-IR較高表達(dá)的DU145細(xì)胞更有效地提高了Docetaxel的生長(zhǎng)抑制效應(yīng)；在DU145裸鼠皮下異種移植瘤模型中,，Lycopene與Docetaxel聯(lián)用比單獨(dú)使用Docetaxel能提高38%的抗瘤療效(P=.047),；從分子機(jī)制來看，首次揭示了Lycopene可通過抑制IGF-I的刺激以及增加IGF-BP3的分泌表達(dá)從而抑制IGF-IR活性,，而且也能抑制下游的Akt激酶活性和Survivin的表達(dá)從而導(dǎo)致細(xì)胞凋亡,。
上述研究揭示了Lycopene與Docetaxel的組合在胰島素樣生長(zhǎng)因子I受體較高表達(dá)的去勢(shì)難治性前列腺癌治療中的臨床意義。該研究結(jié)果為前列腺癌的預(yù)防與臨床治療奠定了物質(zhì)基礎(chǔ)與分子機(jī)制,。相關(guān)論文發(fā)表在NEOPLASIA上,。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
