Yu A, Somasundar P, Balsubramaniam A, Rose A T, Vona-Davis L, McFadden D W
Department of Surgery, Robert C. Byrd Health Sciences Center, Morgantown, West Virginia 26506-9238, USA.
J Surg Res. 2002 Jun 1;105(1):65-8. doi: 10.1006/jsre.2002.6454.
A biologically active form of vitamin E, alpha-tocopherol succinate (ATS), has been shown to induce apoptosis of hormone-refractory prostate cancer in vitro and inhibit cell growth in vivo. The gastrointestinal hormone peptide YY (PYY) has growth inhibitory activity against multiple cancer cell lines and is synergistic with ATS against breast and pancreatic cancer growth. BA-129, a specific Y4 receptor agonist, has growth inhibitory effects on pancreatic cancer in vitro. We investigated the effects of BA-129 and ATS on prostate cancer growth and evaluated their effects on vascular endothelial growth factor (VEGF) production.
A hormone-refractory human prostate cancer cell line, PC-3, was treated with ATS alone at 10 pg/ml, PYY or BA-129 alone at doses of 75 and 500 pmol/ml, or a combination of the two agents. Cell growth was measured by MTT assay and hemocytometry using trypan blue. Quantitative measurement of VEGF was performed by ELISA. Statistical analysis was achieved by ANOVA.
ATS exhibited significant (P < 0.05) growth inhibitory effects in prostate cancer cells. PYY also inhibited growth (P < 0.05). ATS treatment reduced VEGF production (P < 0.05). PYY treatment increased VEGF. When ATS was given in combination with BA-129, VEGF production was further reduced (P < 0.05).
Both PYY and ATS inhibit growth in hormone-refractory prostate cancer, with augmentation when used in combination. VEGF production is inhibited by vitamin E, but increased by PYY. ATS abolishes the augmented VEGF response to PYY. Our data suggest that PYY is involved in the regulation of VEGF production and prostate cancer growth.
维生素E的一种生物活性形式，α-生育酚琥珀酸酯（ATS），已被证明在体外可诱导激素难治性前列腺癌细胞凋亡，并在体内抑制细胞生长。胃肠激素肽YY（PYY）对多种癌细胞系具有生长抑制活性，并且与ATS协同抑制乳腺癌和胰腺癌的生长。BA - 129，一种特异性Y4受体激动剂，在体外对胰腺癌具有生长抑制作用。我们研究了BA - 129和ATS对前列腺癌生长的影响，并评估了它们对血管内皮生长因子（VEGF）产生的作用。
用10 pg/ml的ATS单独处理激素难治性人前列腺癌细胞系PC - 3，用75和500 pmol/ml剂量的PYY或BA - 129单独处理，或两种药物联合处理。通过MTT法和使用台盼蓝进行血细胞计数来测量细胞生长。通过ELISA对VEGF进行定量测定。采用方差分析进行统计分析。
ATS在前列腺癌细胞中表现出显著（P < 0.05）的生长抑制作用。PYY也抑制生长（P < 0.05）。ATS处理降低了VEGF的产生（P < 0.05）。PYY处理增加了VEGF。当ATS与BA - 129联合使用时，VEGF的产生进一步降低（P < 0.05）。
PYY和ATS均抑制激素难治性前列腺癌的生长，联合使用时作用增强。维生素E抑制VEGF的产生，但PYY使其增加。ATS消除了PYY引起的VEGF反应增强。我们的数据表明PYY参与了VEGF产生和前列腺癌生长的调节。
