4月11日,，PLos One在線發(fā)表了中科院生化與細(xì)胞所劉新垣院士研究組關(guān)于“靶向前列腺癌的基因-病毒特異性治療”（Cancer Targeting-Gene-ViroTherapy specific for Prostate Cancer, CTGVT-PCa）策略的最新研究成果,。
前列腺癌是男性泌尿生殖系統(tǒng)腫瘤中最重要的一種,，據(jù)估計(jì),，2010年美國有191533例前列腺癌新發(fā)病例和26329例死亡病例,，超過肺癌,，居男性癌癥之首,。我國前列腺癌的發(fā)病率遠(yuǎn)較歐美國家低，但最近趨勢也較嚴(yán)重,，應(yīng)該深切關(guān)注,。
丁苗同學(xué)的研究是對原來CTGVT的一種修飾，她所構(gòu)建的“Ad-DD3-E1A-WPRE-E1B(Δ55)-gene”是以前列腺癌特異性啟動(dòng)子DD3驅(qū)動(dòng)前列腺特異性抗癌基因PTEN的表達(dá),，所以對前列腺癌具有較強(qiáng)的特異殺傷,，比對肝癌或其它癌癥的殺傷能力更大，是前列腺癌特異性抗癌策略,，故名為CTGVT-PCa（prostate cancer）。此外,，還加入了對RNA起穩(wěn)定作用的WPRE,，提高E1A的表達(dá)量，提高對前列腺癌的殺傷力,，所以對前列腺癌取得了較好的抗癌效果,。
CTGVT是將抗癌基因加入到溶瘤病毒（oncolytic virus，OV）中構(gòu)建而成,，故也叫OV-gene治療,。過去OV與gene都是分開研究的，只有CTGVT才把二者結(jié)合起來了,，OV是一種能靶向癌癥并能在癌細(xì)胞中復(fù)制的溶瘤病毒載體,，此載體能在癌細(xì)胞復(fù)制數(shù)百倍,，則插入其中的抗癌基因也隨之復(fù)制數(shù)百倍，故抗癌效果要增大數(shù)十倍,，所以CTGVT是一種很好,，很有前景的抗癌策略，目前也得到國際上的認(rèn)可,，而丁苗同學(xué)的工作又對此作了改進(jìn),，構(gòu)造了前列腺癌特異的抗癌策略（即CTGVT-PCa）。
該課題得到了國家重點(diǎn)基礎(chǔ)研究發(fā)展計(jì)劃（973計(jì)劃）,、國家自然科學(xué)基金項(xiàng)目,、中國科學(xué)院知識(shí)創(chuàng)新工程重要方向項(xiàng)目、上海市科委項(xiàng)目和浙江理工大學(xué)的經(jīng)費(fèi)支持,。（生物谷Bioon.com）
doi:10.1371/journal.pone.0035153
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PMID:
Prostate Cancer-Specific and Potent Antitumor Effect of a DD3-Controlled Oncolytic Virus Harboring the PTEN Gene
Miao Ding, Xin Cao, Hai-neng Xu, Jun-kai Fan, Hong-ling Huang, Dong-qin Yang1, Yu-hua Li, Jian Wang, Runsheng Li, Xin-Yuan Liu
Prostate cancer is a major health problem for men in Western societies. Here we report a Prostate Cancer-Specific Targeting Gene-Viro-Therapy (CTGVT-PCa), in which PTEN was inserted into a DD3-controlled oncolytic viral vector (OV) to form Ad.DD3.E1A.E1B(Δ55)-(PTEN) or, briefly, Ad.DD3.D55-PTEN. The woodchuck post-transcriptional element (WPRE) was also introduced at the downstream of the E1A coding sequence, resulting in much higher expression of the E1A gene. DD3 is one of the most prostate cancer-specific genes and has been used as a clinical bio-diagnostic marker. PTEN is frequently inactivated in primary prostate cancers, which is crucial for prostate cancer progression. Therefore, the Ad.DD3.D55-PTEN has prostate cancer specific and potent antitumor effect. The tumor growth rate was almost completely inhibited with the final tumor volume after Ad.DD3.D55-PTEN treatment less than the initial volume at the beginning of Ad.DD3.D55-PTEN treatment, which shows the powerful antitumor effect of Ad.DD3.D55-PTEN on prostate cancer tumor growth. The CTGVT-PCa construct reported here killed all of the prostate cancer cell lines tested, such as DU145, 22RV1 and CL1, but had a reduced or no killing effect on all the non-prostate cancer cell lines tested. The mechanism of action of Ad.DD3.D55-PTEN was due to the induction of apoptosis, as detected by TUNEL assays and flow cytometry. The apoptosis was mediated by mitochondria-dependent and -independent pathways, as determined by caspase assays and mitochondrial membrane potential.
