Scaife Courtney L, Kuang Jinqiu, Wills Jason C, Trowbridge D Brad, Gray Phil, Manning Bernadette M, Eichwald Ernst J, Daynes Raymond A, Kuwada Scott K
Department of Surgery, Salt Lake City Veterans Administration Medical Center, and University of Utah, Salt Lake City, Utah 84132, USA.
Cancer Res. 2002 Dec 1;62(23):6870-8.
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.
转录因子核因子κB（NFκB）在多种癌细胞中呈组成性激活，并调节多个抗凋亡基因的表达。先前的研究表明，在小鼠中采用转基因方法抑制NFκB在癌症治疗中具有作用。我们发现，在结肠癌细胞重新黏附过程中，NFκB被短暂激活，其激活程度远高于背景组成性水平，这使得重新黏附的结肠癌细胞在存在可溶性NFκB抑制剂的情况下极易发生凋亡。这些化合物在体内转移接种模型中大大减少了结肠癌细胞的植入。可溶性NFκB抑制剂显著诱导重新黏附的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药物。
