小说组合抗代谢物,助教- 102,展品抗肿瘤活性在人类癌症细胞通过一种机制涉及FU-resistant FTD结合在DNA。

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铃木Emura T, N,山口M, Ohshimo H,福岛

小说组合抗代谢物,助教- 102,展品抗肿瘤活性在人类癌症细胞通过一种机制涉及FU-resistant FTD结合在DNA。

Int J杂志。2004年9月,25 (3):571 - 8。

PubMed ID

15289858 (在PubMed

]

文摘

助教- 102是一种新的抗代谢物代理组成的α,α,alpha-trifluorothymidine (FTD;1米)和胸苷磷酸化酶抑制剂(TPI;0.5 M)。在这里,我们研究了助教的抗肿瘤效应和机制对研究者用- 102,或FdUrd,抵抗人类癌症细胞系。通过各自的肿瘤生长抑制率对5-FU-resistant FTD NUGC-3约70%在剂量200毫克/公斤/天;这个值是与父母NUGC-3。另一方面,研究者用的肿瘤抑制率,对5-FU-resistant FdUrd, TS-1 NUGC-3低于反对父母NUGC-3。类似的观察是在一个FdUrd-resistant人类结肠癌细胞系(DLD-1)。助教- 102也有效5-FU-less敏感人类胰腺癌细胞系(PAN-12和BxPC-3)和人类食道癌(电汇)相比,研究者用或UFT。我们的假设是相对较短和高剂量的助教- 102结果在一个额外的FTD机制纳入DNA除了thymidylate合成酶(TS)的抑制作用。然后我们检查了FTD对DNA在细胞水平上的影响。 After treatment with FTD or FdUrd, the DNA fragmentation pattern was examined using filter elution and in situ nick translation. Treatment with FTD for 2 h resulted in marked DNA fragmentation. When the tumor cells were treated with FTD for 72 h or with FdUrd for 2 or 72 h, only a small amount of DNA fragmentation was observed, and the appearance of the tumor cells did not differ markedly from that of untreated cells. Moreover, the DNA fragmentation rate in the TAS-102 treatment group was significantly higher than that in the control group in vivo. These results suggest that when tumor cells are exposed to high concentrations of FTD for short periods of time, FTD manifests its antitumor activity primarily through the induction of DNA fragmentation after FTD incorporation into the DNA. We conclude that TAS-102 is expected to manifest antitumor effects against 5-FU-resistant tumors that are similar to those exerted in 5-FU-sensitive tumors.

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药物

助教- 102