Preventive effect of matrix metalloproteinase inhibitor, R-94138, in combination with mitomycin C or cisplatin on peritoneal dissemination of human gastric cancer cell line TMK-1 in nude mice.

Preventive effect of matrix metalloproteinase inhibitor, R-94138, in combination with mitomycin C or cisplatin on peritoneal dissemination of human gastric cancer cell line TMK-1 in nude mice.
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DOI:
10.1111/j.1349-7006.1999.tb00674.x
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发表时间:
1999-01
期刊:
Japanese journal of cancer research : Gann
影响因子:
--
通讯作者:
Kitajima M
Kitajima M
中科院分区:
其他
文献类型:
--
作者:
Igarashi N;Kubota T;Otani Y;Matsuzaki SW;Watanabe M;Teramoto T;Kumai K;Tamaki K;Tanzawa K;Kobayashi T;Kitajima M

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研究了基质金属蛋白酶抑制剂R-94138预防人胃癌异种移植物TMK-1腹膜播散的能力。当对TMK-1细胞和人正常成纤维细胞的共培养物的上清液进行明胶酶谱分析时,很明显,MMP-2的蛋白表达已被R-94138抑制。当腹膜内(i. p.)以5×105个细胞/只的剂量植入裸小鼠体内,产生的腹膜传播模拟临床癌性腹膜炎。当在肿瘤接种后12小时给予最大耐受剂量的丝裂霉素C(MMC)或顺铂(DDP)时,腹膜播散被完全抑制,而当以20 mg/kg的剂量i. p.以q.d.给药时,R-94138的作用有限。肿瘤注射后12 h开始×5。MMC和DDP在肿瘤接种后1周以2和3 mg/kg i. p.的单次剂量给药时也抑制腹膜播散,分别当以30 mg/kg剂量i. p.给药时,R-94138抑制腹膜播散,给药方案为q.d.。从肿瘤注射后1周开始×5。MMC和R-94138联合使用增加了对腹膜播散的预防作用。R-94138似乎是预防胃癌腹膜转移的有希望的候选药物。
R‐94138, a matrix metalloproteinase inhibitor, was examined for the ability to prevent peritoneal dissemination of a human gastric cancer xenograft, TMK‐1. When the supernatant of a co‐culture of TMK‐1 cells and human normal fibroblast cells was subjected to gelatin zymography, it was clear that the protein expression of MMP‐2 had been inhibited by R‐94138. When TMK‐1 was injected intraperitoneally (i.p.) into nude mice at 5×105 cells/body, the resulting peritoneal dissemination mimicked clinical carcinomatous peritonitis. When the maximum tolerated dose of mitomycin C (MMC) or cisplatin (DDP) was given 12 h after the tumor inoculation, peritoneal dissemination was completely inhibited, while the effect of R‐94138 was limited when it was given i.p. at a dose of 20 mg/kg in a schedule of q.d. ×5 starting 12 h after tumor injection. MMC and DDP also suppressed peritoneal dissemination when they were administered 1 week after the tumor inoculation at a single dose of 2 and 3 mg/kg i.p., respectively. R‐94138 inhibited peritoneal dissemination when it was administered i.p. at a dose of 30 mg/kg in a schedule of q.d. ×5 starting from 1 week after tumor injection. The combination of MMC and R‐94138 increased the preventive effect on peritoneal dissemination. R‐94138 seems to be a promising candidate to prevent peritoneal dissemination of gastric cancer.
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