Nuclear factor kappaB inhibitors induce adhesion-dependent colon cancer apoptosis: implications for metastasis.
Nuclear factor kappaB inhibitors induce adhesion-dependent colon cancer apoptosis: implications for metastasis.
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发表时间：
2002-12
期刊：
影响因子：
11.2
通讯作者：
C. Scaife;Ji-sun Kuang;Jason C. Wills;D. B. Trowbridge;Phillip D. Gray;B. Manning;E. Eichwald;R. Daynes;S. Kuwada
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文献类型：
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作者：
C. Scaife;Ji-sun Kuang;Jason C. Wills;D. B. Trowbridge;Phillip D. Gray;B. Manning;E. Eichwald;R. Daynes;S. Kuwada
转录因子核因子κ B（NF κ B）在许多类型的癌细胞中具有组成性活性，并调节几种抗凋亡基因的表达。先前的研究证明了在小鼠中使用转基因方法抑制NF κ B在癌症治疗中的作用。我们发现，在结肠癌细胞再粘附过程中，NF κ B的瞬时激活远远大于背景组成水平，这使得再粘附的结肠癌细胞在可溶性NF κ B抑制剂存在下对凋亡非常敏感。这些化合物大大减少了转移的体内接种模型中的结肠癌细胞植入。可溶性NF κ B抑制剂显著诱导可移植结肠癌细胞凋亡的能力使其成为预防结肠癌转移的潜在候选者。
The transcription factor nuclear factor kappaB (NFkappaB) is constitutively active in many types of cancercells and regulates the expression of several antiapoptotic genes. Previous studies demonstrated a role for the inhibition of NFkappaB in cancer therapyusing a transgenic approach in mice. We found that NFkappaB was transiently activated much greater than background constitutive levels during colon cancer cell readhesion, which rendered the readhering colon cancer cells exquisitely susceptible to apoptosis in the presence of soluble NFkappaB inhibitors. These compounds greatly reduced colon cancer cell implantation in an in vivo seeding model of metastasis. The ability of soluble NFkappaB inhibitors to significantly induce apoptosis of readherent colon cancer cells makes them prospective candidates for preventing colon cancer metastasis.