CYTOSTATIC AND CYTO-TOXIC EFFECTS OF PANNON (P-30 PROTEIN), A NOVEL ANTICANCER AGENT
CYTOSTATIC AND CYTO-TOXIC EFFECTS OF PANNON (P-30 PROTEIN), A NOVEL ANTICANCER AGENT
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DOI：
10.1111/j.1365-2184.1988.tb00855.x
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发表时间：
1988-05-01
期刊：
影响因子：
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通讯作者：
SHOGEN, K
中科院分区：
文献类型：
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作者：
DARZYNKIEWICZ, Z;CARTER, SP;SHOGEN, K
P-30蛋白是一种新的蛋白质，分子量约为15 kD，从脊椎动物组织提取物中获得，显示出体内抗肿瘤活性。在体外对人白血病HL-60、人颌下癌A-253、人结肠腺癌科洛320 CM和鼠红白血病（Friend白血病）细胞系研究了本品纯化形式（P-30蛋白）或部分纯化提取物（Pannon）的细胞抑制和细胞毒性作用。其中HL-60、A-253和科洛320 CM细胞对本药敏感，而Friend白血病细胞对本药耐药。这些作用具有时间和浓度依赖性。在处理的最初24-48小时期间，细胞增殖明显减缓，但细胞死亡并不广泛。24-48 h后，细胞周期S期细胞比例减少，细胞优先停滞在G1期。G1细胞表现出高度异质性相对于RNA含量和一些细胞的特征是非常低的RNA含量。进行性细胞死亡发生在与Pannon保持长达7天的培养物中，与其浓度成比例。在0.13和1.5 μ g/ml该蛋白存在下，在A-53细胞生长期间，观察到A-53细胞的克隆形成分别减少50%和90%。指数生长的细胞比汇合培养的细胞对Pannon更敏感。与对照集落相比，在Pannon存在下生长的A-253细胞集落的大小要小得多，表明克隆原的增殖速率被该试剂降低。似乎p-30蛋白通过调节细胞向静止或分化的转变而诱导细胞生长抑制作用。其细胞毒活性的机制尚不清楚。
P-30 Protein is a novel protein, of molecular weight approximately 15 kD, obtained from the extract of a vertebrate tissue showing in vivo antitumour activity. Cytostatic and cytotoxic effects of this product in its purified form (P-30 Protein) or in partially purified extracts (Pannon) were studied in vitro on human leukaemia HL-60, human submaxillary carcinoma A-253, human colon adenocarcinoma Colo 320 CM and murine erythroleukaemia (Friend leukaemia) cell lines. Of these cells, HL-60, A-253 and Colo 320 CM were sensitive and Friend leukaemia resistant to this agent. The effects were time- and concentration-dependent. During the initial 24-48 h of treatment, a slowdown in cell proliferation was apparent but cell death was not extensive. After 24-48 h, there was a reduction in the proportion of cells in S phase of the cell cycle and the cells became preferentially arrested in G1 phase. The G1 cells showed high heterogeneity with respect to RNA content and some cells were characterized by very low RNA content. Progressive cell death occurred in cultures maintained with Pannon for up to 7 d in proportion to its concentration. Reductions of 50 and 90% in clonogenicity of A-53 cells were observed during their growth in the presence of 0.13 and 1.5 .mu.g/ml of this protein, respectively. Exponentially growing cells were more sensitive to Pannon compared with cells from confluent cultures. Colonies of A-253 cells growing in the presence of Pannon were much smaller in size compared with control colonies, indicating that the rate of proliferation of clonogens is reduced by this agent. It appears that p-30 Protein induces cytostatic effects via modulation of cell transition to quiescence or differentiation. The mechanism of its cytotoxic activity is unclear.