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干扰素-γ和α2a与肿瘤细胞的特异性结合及其抗肿瘤活性。

Specific binding of interferon-gamma and -alpha 2a to tumor cells and their antitumor activities.

作者信息

Ishii Y, Tsukagoshi S

机构信息

Cancer Institute Hospital, Tokyo, Japan.

出版信息

J Pharmacobiodyn. 1988 Jul;11(7):465-71. doi: 10.1248/bpb1978.11.465.

Abstract

Binding activities of a recombinant human interferon-gamma (IFN-gamma) preparation with 5 human tumor cell lines, including lung large cell carcinoma PC-13, lung small cell carcinoma QG-90, amelanotic melanoma HMV-1, renal carcinoma ACHN and Burkitt lymphoma Daudi, were compared with those of IFN-alpha 2a. Three out of five human tumor cell lines, ACHN, HMV-1, and QG-90, were highly susceptible to IFN-gamma: the concentrations required to inhibit 50% of the growth of cells (IC50) of ACHN, HMV-1, and QG-90 were 26, 11 and 7 pM, respectively. IFN-alpha 2a also markedly inhibited the growth of ACHN, HMV-1 and Daudi cells: the values of IC50 for the former and latter cells were 20, 31 and 0.8 pM, respectively. With these susceptible cells, larger amounts of IFN-gamma were bound than with resistant cells. On the other hand, IFN-alpha 2a bound all cell lines, irrespective of the susceptibilities of cells. The values of the apparent dissociation constant (Kd) of binding of both IFNs ranged from 1.3 to 7.3 x 10(-10) M. The competitive binding test revealed that the binding properties of IFN-gamma were different from those of IFN-alpha 2a. Under the present experimental condition, it could be said that, with IFN-gamma, the susceptibilities of cells were linked of the expression of the receptors, but there were some exceptions with IFN-alpha 2a.

摘要

将重组人干扰素-γ(IFN-γ)制剂与5种人类肿瘤细胞系(包括肺大细胞癌PC-13、肺小细胞癌QG-90、无色素黑色素瘤HMV-1、肾癌ACHN和伯基特淋巴瘤Daudi)的结合活性与IFN-α 2a的结合活性进行了比较。5种人类肿瘤细胞系中的3种,即ACHN、HMV-1和QG-90,对IFN-γ高度敏感:ACHN、HMV-1和QG-90抑制50%细胞生长所需的浓度(IC50)分别为26、11和7 pM。IFN-α 2a也显著抑制ACHN、HMV-1和Daudi细胞的生长:前两种细胞和后一种细胞的IC50值分别为20、31和0.8 pM。对于这些敏感细胞,与抗性细胞相比,IFN-γ的结合量更大。另一方面,IFN-α 2a与所有细胞系结合,而不考虑细胞的敏感性。两种干扰素结合的表观解离常数(Kd)值范围为1.3至7.3×10⁻¹⁰ M。竞争性结合试验表明,IFN-γ的结合特性与IFN-α 2a不同。在当前实验条件下,可以说,对于IFN-γ,细胞的敏感性与受体的表达相关,但对于IFN-α 2a存在一些例外情况。

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