Parnaud G, Corpet D E, Gamet-Payrastre L
Laboratoire des Xénobiotiques, Institut National de la Recherche Agronomique, Toulouse, France.
Int J Cancer. 2001 Apr 1;92(1):63-9. doi: 10.1002/1097-0215(200102)9999:9999<::AID-IJC1158>3.0.CO;2-8.
Polyethylene glycol (PEG 8000) is a potent cancer chemopreventive agent. This osmotic laxative polymer markedly suppresses colon cancer in rats. To explain the mechanism, we have tested the in vitro effect of PEG on four human cell lines. Two poorly differentiated adenocarcinoma lines (HT29 and COLO205), a fetal mucosa line (FHC) and a differentiated line (post-confluent Caco-2) were incubated with various PEG concentrations for 2-5 days. Results show that PEG markedly and dose-dependently inhibited HT29 and COLO205 cell growth. This cytostatic effect was associated with a blocking of the cell cycle in G0/G1 phase. In addition, PEG decreased the viability of HT29 and COLO205 adenocarcinoma cells. In contrast, post-confluent intestinal-like Caco-2 cells and normal FHC cells were, respectively, not or little affected by PEG. Moreover, the lactate concentration increased twofold in the medium of PEG-treated HT29 cells compared with untreated cells. Microscopic observations showed that PEG induced cell shrinking, membrane blebbing and the condensation of nuclear chromatin. However, because no DNA ladder and no annexin staining were detected, we presume that PEG did not induce apoptosis. PEG increased the osmotic pressure of the culture medium. Hyperosmotic media with added NaCl or sorbitol also inhibited HT29 cell growth, and increased lactate release. These results suggest that PEG may be selectively cytostatic for proliferating cancer cells. This growth inhibition may be due to the high osmotic pressure induced by PEG in vitro. Because the osmotic pressure is high in feces of PEG-fed rats, it may explain the suppression of colon carcinogenesis by PEG.
聚乙二醇（PEG 8000）是一种有效的癌症化学预防剂。这种渗透性泻药聚合物能显著抑制大鼠结肠癌。为了解释其作用机制，我们测试了PEG对四种人类细胞系的体外作用。将两种低分化腺癌细胞系（HT29和COLO205）、一种胎儿黏膜细胞系（FHC）和一种分化细胞系（汇合后的Caco-2）与不同浓度的PEG孵育2 - 5天。结果表明，PEG显著且呈剂量依赖性地抑制HT29和COLO205细胞的生长。这种细胞生长抑制作用与细胞周期在G0/G1期的阻滞有关。此外，PEG降低了HT29和COLO205腺癌细胞的活力。相比之下，汇合后的肠样Caco-2细胞和正常FHC细胞分别不受PEG影响或受其影响较小。而且，与未处理的细胞相比，经PEG处理的HT29细胞培养基中的乳酸浓度增加了两倍。显微镜观察显示，PEG诱导细胞皱缩、细胞膜起泡和核染色质凝聚。然而，由于未检测到DNA梯状条带和膜联蛋白染色，我们推测PEG未诱导细胞凋亡。PEG增加了培养基的渗透压。添加了NaCl或山梨醇的高渗培养基也抑制HT29细胞生长，并增加乳酸释放。这些结果表明，PEG可能对增殖的癌细胞具有选择性细胞生长抑制作用。这种生长抑制可能是由于PEG在体外诱导的高渗透压所致。由于喂食PEG的大鼠粪便中渗透压较高，这可能解释了PEG对结肠癌发生的抑制作用。
