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 末端碱度比传统的人 TNF-α 更高，对肿瘤细胞具有更广泛的细胞毒性，并且比 TNF-α 的毒性更小。我们研究了 TNF-S 对人的抗肿瘤作用。我们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一起培养时几乎没有观察到细胞抑制作用，但是在含有由THP-1细胞和重组TNF-Scwl产生的TNF-S的细胞系上观察到高十到一百倍的细胞抑制作用。由于rTNF-Scwl的产量相当低，因此对rTNF-Scw2和rTNF-Sam2进行了针对T-24的细胞毒性作用的进一步分析。 rTNF-Scw2 对 T-24 的作用高于 TNF-α，但低于 rTNF-Scwl。18 小时后，在低于 1,000 u/ml 的情况下，未发现 rTNF-Scw2 对 T-24 的细胞毒性作用。通过分别添加 Act-D、Act-D、 ADM、MMG和CDDP似乎在体外对泌尿系癌细胞的细胞毒性作用不充分，与体外结果相反，单独使用时膀胱癌异种移植物的生长显着减慢。通过联合治疗，在同一异种移植物中观察到 TNF-S 和 CDDP 的联合作用高于单独施用 cDDP 的效果。嵌合蛋白胸腺素β4/TNF-S与香菇多糖瘤内注射后，前列腺癌异种移植物得到部分消退，根据体内结果，我们怀疑TNF-S对人类泌尿肿瘤有一定的治疗效果，且该疗效可能是可行的。可以通过额外的抗癌剂或其他生物反应调节剂来增强。