Induction of multinucleated cells and apoptosis in the PC-3 prostate cancer cell line by low concentrations of polyethylene glycol 1000
Induction of multinucleated cells and apoptosis in the PC-3 prostate cancer cell line by low concentrations of polyethylene glycol 1000
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DOI：
10.1111/j.1349-7006.2008.00781.x
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发表时间：
2008-05-01
期刊：
影响因子：
5.7
通讯作者：
Nakagama, Hitoshi
中科院分区：
文献类型：
--
作者：
Fukuta, Katsuhiro;Kohri, Kenjiro;Nakagama, Hitoshi
据报道，聚乙二醇（PEG）经口给药可抑制致癌剂处理大鼠结肠病变的发展。然而，PEG的化学预防活性的精确机制在很大程度上仍然难以捉摸。基于PEG作为“融合剂”的特征，我们通过在PC-3前列腺癌细胞中诱导多核细胞形成和诱导凋亡来研究其作为化疗剂的潜力。当PC-3细胞用0.5和1.0%PEG 1000处理时，在体外高细胞密度（100 μ L PEG溶液中1 × 10（6）个细胞）下PEG处理后36 h，多核细胞的诱导频率分别为8.4和13%。尽管PEG处理的PC-3细胞中细胞周期进程的异常不明显，但由于凋亡，多核细胞在38 h左右基本上消失。相比之下，当PC-3细胞以低得多的细胞密度暴露于高达1.0%PEG时，即在普通培养条件下，未观察到明显的生长抑制。此外，与磷酸盐缓冲盐水注射相比，将0.5% PEG溶液体内注射到植入BALB/c-nu/nu雄性小鼠的PC-3异种移植物中显著抑制肿瘤生长。在PEG注射的肿瘤内观察到多核TdT介导的dUTP-生物素缺口末端标记（TUNEL）阳性细胞。本文证明PEG通过诱导凋亡（可能通过细胞融合）具有抗细胞增殖和抗肿瘤作用。因此，PEG注射疗法可以作为局部前列腺癌的替代化疗策略，包括那些对雄激素剥夺疗法难治的前列腺癌。
Polyethylene glycol (PEG) has been reported to inhibit the development of colonic lesions in carcinogen-treated rats when administered orally. However, the precise mechanism for the chemopreventive activity of PEG remains largely elusive. Based on a characteristic feature of PEG as a 'fusogen', we investigated its potential as a chemotherapeutic agent through the induction of multinucleated cell formation and apoptosis induction in PC-3 prostate cancer cells. When PC-3 cells were treated with 0.5 and 1.0% PEG 1000, multinucleated cells were induced at a frequency of 8.4 and 13%, respectively, 36 h after PEG treatment under high cell density (1 x 10(6) cells in 100 mu L PEG solution) in vitro. Although abnormality of cell cycle progression was not evident in PEG-treated PC-3 cells, multinucleated cells substantially disappeared at around 38 h due to apoptosis. In contrast, no apparent growth suppression was observed when PC-3 cells were exposed to up to 1.0% PEG at a much lower cell density, namely under ordinary culture conditions. Furthermore, injection of 0.5% PEG solution in vivo into PC-3 xenografts implanted in BALB/c-nu/nu male mice significantly suppressed tumor growth compared to phosphate-buffered saline injection. Multinucleated TdT-mediated dUTP-biotin nick end-labeling (TUNEL)-positive cells were observed inside the PEG-injected tumors. PEG was here demonstrated to have anticell proliferation and antitumor effects via induction of apoptosis, possibly by cell fusion. PEG injection therapy could therefore be adopted as an alternative chemotherapeutic strategy for localized prostate cancers, including those that become refractory to androgen-deprivation therapy.