Anti-tumor effect of novel tumor necrosis factor (TNF-S) to human urological cancer in vitro and in vivo

新型肿瘤坏死因子（TNF- s）在n端区比传统的人TNF- α碱度更高，对肿瘤细胞具有更广泛的细胞毒性，而毒性比TNF- α小。我们在体外和体内研究了TNF-S对人泌尿系统癌细胞的抗肿瘤作用。我们使用四种膀胱癌细胞系（T-24, HUB-4， HUB-6和HUB-15）和前列腺癌细胞系PC-3进行体外实验。虽然用高剂量TNF- α培养这些细胞时，细胞抑制作用很小，但在THP-1细胞和重组TNF- scwl（一种rTNF-Ss）产生TNF- s的细胞系上，细胞抑制作用高出10到100倍。由于rTNF-Scwl的产率很低，我们进一步分析了rTNF-Scw2和rTNF-Sam2对T-24的细胞毒性。rTNF-Scw2对T-24的细胞毒作用高于tnf - α，但低于rTNF-Scwl。rTNF-Scw2在低于1000 u/ml的浓度下对T-24无细胞毒作用。分别加入Act-D、ADM、MMG和CDDP四种抗癌剂后，rttf - scw2在1000 u/ml时的细胞毒性略有增加。在体外实验中，TNF-S对泌尿系统癌细胞的细胞毒作用似乎并不充分。与体外结果相反，单一使用TNF-S可显著减缓膀胱癌异种移植物的生长。在同一异种移植物中，TNF-S和CDDP联合使用的效果高于单独使用CDDP的效果。通过联合治疗，8例异种移植物中有3例肿瘤完全消退。当一种嵌合蛋白胸腺素β 4/TNF-S与香菇多糖一起注入瘤内时，前列腺癌异种移植物得到部分消退。根据体内实验结果，我们推测TNF-S对人类泌尿系统肿瘤具有一定的治疗效果，并可能通过添加抗癌药物或其他生物反应调节剂来增强其疗效。少

Novel tumor necrosis factor (TNF-S) with higher basicity than conventional human TNF- alpha in the N-terminal region had showed a broader cytotoxicity to tumor cells and less toxicity than TNF-alpha. We investigated antitumor effects of TNF-S to human urological cancer cells in vitro and in vivo. We used four bladder cancer cell lines (T-24, HUB-4, HUB-6 and HUB-15) and a prostate cancer cell line, PC-3, in vitro. Although little cytostatic effect was seen when these cells were cultured with high dose TNF- alpha, ten to a hundred times higher cytostatic effects were seen on the cell lines with TNF-S produced by THP-1 cells and recombinant TNF-Scwl that was one type of rTNF-Ss. Because of the quite poor yield of rTNF-Scwl, further analyses of cytotoxicity against T-24 were carried out on rTNF-Scw2 and rTNF-Sam2. The cytotoxic effect of rTNF-Scw2 to T-24 was higher than TNF-alpha, but less than rTNF-Scwl. No cytotoxic effect of rTNF-Scw2 to T-24 was found at less than 1,000 u/ml without … More anticancer agents after 18 hours. A slight increase of the cytotoxicity at 1,000 u/ml for rTTiF-Scw2 was found by the respective addition of four anticancer agents that were Act-D, ADM, MMG and CDDP. It seemed that the cytotoxic effect of TNF-S against urological cancer cells was not sufficient in vitro. On the contrary to the in vitro result, there was significant slowing of growth in a bladder cancer xenograft by a singular use of TNF-S. A combination effect of TNF-S and CDDP in the same xenograft was higher than the effect of singular administration of cDDP. Total tumor regression was observed in three of eight xenografts by the combination therapy. When a chimeric protein, Thymosin beta4/TNF-S, was given intrtumorally with Lentinan, prostate cancer xenografts were partially regressed. According to the in vivo results, we suspect that TNF-S has a certain therapeutic efficacy against human urological tumors and the efficacy may be enhanced by the additional anticancer agents or other biological response modifiers. Less