Opioid growth factor regulates the cell cycle of human neoplasias.
Opioid growth factor regulates the cell cycle of human neoplasias.
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DOI：
10.3892/ijo.17.5.1053
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发表时间：
2000-11
影响因子：
5.2
通讯作者：
I. Zagon;C. D. Roesener;M. Verderame;B. M. Ohlsson-Wilhelm;Roger J. Levin;P. McLaughlin
中科院分区：
文献类型：
--
作者：
I. Zagon;C. D. Roesener;M. Verderame;B. M. Ohlsson-Wilhelm;Roger J. Levin;P. McLaughlin
天然阿片样物质生长因子（OGF），[Met 5]-脑啡肽，是一种滋补抑制肽，在发育、癌症、稳态细胞更新、伤口愈合和血管生成过程中调节细胞增殖和迁移以及组织组织形成。OGF作用由OGF受体（OGFr）介导。为了研究OGF对细胞增殖的靶点，在3种人癌细胞系：胰腺癌（BxPC-3）、结肠癌（HT-29）和头颈癌（CAL-27）中检测过量OGF的作用和阿片类拮抗剂纳洛酮（NTX）剥夺OGF-OGFr相互作用。与对照组相比，OGF暴露降低了生长、DNA合成和有丝分裂，并增加了倍增时间。流式细胞仪分析表明，在G 0/G1期细胞的显着增加和细胞的S和G2/M期的补偿减少。与该观察结果一致，标记有丝分裂（PLM）分析的百分比显示G 0/G1期时间显著增加。用NTX受体阻断剂增加了生长速率、DNA合成长度和有丝分裂期，并减少了对照值的倍增时间。流式细胞仪分析表明S期和G2/M期细胞比例增加，G 0/G1期细胞数量减少。PLM评估显示3种细胞系中S和G2期长度缩短，并且在一些癌症中M和G 0/G1期减少。这些结果表明，OGF的作用是针对G 0/G1期，但OGF-OGFr接口中断对细胞周期有广泛的影响。在对数期生长期间阻断OGF-OGFr的数据表明生长肽及其受体在细胞周期中的必要护送。
The native opioid growth factor (OGF), [Met5]-enkephalin, is a tonic inhibitory peptide that modulates cell proliferation and migration, as well as tissue organization, during development, cancer, homeostatic cellular renewal, wound healing, and angiogenesis. OGF action is mediated by the OGF receptor (OGFr). To investigate the target of OGF as to cell proliferation, the effects of excess OGF, and a deprivation of OGF-OGFr interaction by an opioid antagonist, naltrexone (NTX), were examined in 3 human cancer cell lines: pancreatic (BxPC-3), colon (HT-29), and head and neck (CAL-27). OGF exposure decreased growth, DNA synthesis, and mitosis, and increased the doubling time from control levels. FACS analysis revealed a marked increase in cells in the G0/G1 phase and compensatory reduction in cells in S and G2/M phases. Consistent with this observation, the percentage of labeled mitosis (PLM) analysis showed a notable increase in the time of the G0/G1 phase. Receptor blockade with NTX increased the rate of growth, length of DNA synthesis and mitotic phases, and decreased doubling time from control values. FACS analysis indicated an increase in the proportion of cells in S and G2/M phases, and a decrease in the number of cells in the G0/G1 phase. PLM evaluation demonstrated a shortening of the length of the S and G2 phases in the 3 cell lines, and decreases in the M and G0/G1 phases in some cancers. These results indicate that OGF action is directed at the G0/G1 phase, but interruption of OGF-OGFr interfacing has widespread repercussions on the cell cycle. The data on blockade of OGF-OGFr during log phase growth suggest a requisite escorting of the growth peptide and its receptor through the cell cycle.