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）对人泌尿癌的体外和体内抗肿瘤作用

• 批准号: 63570755
• 负责人: KATO Mikio
• 金额: $ 1.22万
• 依托单位: Saitama Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570755/
• 关键词: Novel TNF; Human urological cancer; Antitumor effect; 腫瘍壊死因子; 人尿路系悪性腫瘍; ヌードマウス移植系; 増殖抑制

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

新型肿瘤坏死因子（TNF-S）的N端碱性高于传统的人TNF-α，对肿瘤细胞具有更广泛的细胞毒性，毒性低于TNF-α。我们研究了TNF-S对人泌尿系肿瘤细胞的体内外抗肿瘤作用。我们在体外使用了四种膀胱癌细胞系（T-24、HUB-4、HUB-6和HUB-15）和前列腺癌细胞系PC-3。虽然当这些细胞与高剂量TNF-α一起培养时观察到很少的细胞抑制作用，但是在具有由THP-1细胞产生的TNF-S和重组TNF-Scwl（其为一种类型的rTNF-Ss）的细胞系上观察到十至一百倍的细胞抑制作用。由于rTNF-Scwl的产率相当低，因此对rTNF-Scw 2和rTNF-Sam 2进行针对T-24的细胞毒性的进一步分析。rTNF-Scw 2对T-24的细胞毒作用高于TNF-α，但低于rTNF-Scw 1。rTNF-Scw 2在低于1,000 u/ml时对T-24细胞无细胞毒作用， ...更多信息 18小时后的抗癌药物。分别加入Act-D、ADM、MMG和CDDP四种抗癌药物后，发现rTTiF-Scw 2的细胞毒性在1，000 u/ml时略有增加。TNF-S在体外对泌尿系肿瘤细胞的杀伤作用不明显。与体外结果相反，通过单独使用TNF-S，膀胱癌异种移植物的生长显著减慢。TNF-S和CDDP在同一异种移植物中的联合作用高于单独施用cDDP的作用。通过联合治疗，在8个异种移植物中的3个中观察到总肿瘤消退。当肿瘤内给予嵌合蛋白胸腺素β 4/TNF-S与香菇多糖时，前列腺癌异种移植物部分消退。根据体内结果，我们怀疑TNF-S对人类泌尿系统肿瘤具有一定的治疗功效，并且这种功效可能会通过额外的抗癌药物或其他生物反应调节剂来增强。少