Mechanisms underlying apoptosis induced by combination of 5-fluorouracil and interferon-gamma
Mechanisms underlying apoptosis induced by combination of 5-fluorouracil and interferon-gamma
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DOI：
10.1006/bbrc.1997.7657
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发表时间：
1997-11-17
影响因子：
3.1
通讯作者：
Ikehara, S
中科院分区：
文献类型：
--
作者：
Koshiji, M;Adachi, Y;Ikehara, S
一些研究人员报道了5-氟尿嘧啶(5-FU)或5-氟尿嘧啶(5-FU)联合干扰素-γ(干扰素-γ)治疗晚期结直肠癌的临床疗效。也有报道称，5-FU诱导细胞凋亡是由于其对DNA合成和功能RNA合成的影响。在本研究中，我们使用结肠癌细胞系Colo 201，研究了5-FU或5-FU与干扰素-伽马联合应用的生物学机制。5-FU和干扰素-γ以剂量和时间依赖的方式单独或相加诱导COLO 201细胞凋亡，并与Bcl2表达下调和Bax表达上调相关。白介素1β转换酶(ICE)样的蛋白水解酶抑制剂(但不是ICE抑制剂)可阻断5-FU诱导的细胞凋亡。这些结果表明，5-FU具有诱导COLO 201细胞凋亡的作用，其机制可能与上调Bax的表达有关；5-FU诱导细胞凋亡的信号与干扰素-γ不同。因此，5-FU和干扰素-γ在诱导细胞凋亡方面具有额外的作用。这一发现为临床应用5-FU和/或干扰素-γ治疗结直肠癌提供了实验依据。(C)1997年学术出版社。
Several investigators have reported on the clinical effects of 5-fluorouracil (5-FU) or the combination of 5-FU plus interferon-gamma (IFN-gamma) on patients with advanced colorectal carcinoma. It has also been reported that apoptosis induced by 5-FU is due to the effects on DNA synthesis and functional RNA synthesis. In the present study, we examine the biological mechanisms underlying 5-FU or the combination of 5-FU plus IFN-gamma, using the colorectal carcinoma cell Line, COLO 201. 5-FU and IFN-gamma independently or additively induced apoptosis in COLO 201 in a dose-and time-dependent manner, which was correlated with the down-regulation of Bcl-2 and the up-regulation of Bax. An interleukin-1 beta-converting enzyme (ICE)-like protease inhibitor (but not an ICE-inhibitor) blocked apoptosis induced by only 5-FU. These results suggest that 5-FU has the capacity to induce apoptosis in COLO 201, resulting from the upregulation of Bax; the apoptosis-inducing signal of 5-FU seems to be different from that of IFN-gamma. Thereby, 5-FU and IFN-gamma have additional effects on the induction of apoptosis. This finding provides an experimental basis for clinical therapy using 5-FU and/or IFN-gamma for colorectal cancer. (C) 1997 Academic Press.