Inhibition of NF-kappaB, clonogenicity, and radiosensitivity of human cancer cells.
نویسندگان
چکیده
BACKGROUND Activation of the transcription factor NF-kappaB is part of the immediate early response of tissues to ionizing irradiation. This pathway has been shown to protect cells from tumor necrosis factor-alpha, chemotherapy, and radiation therapy-induced apoptosis (programmed cell death). However, because the role of NF-kappaB as a modifier of the intrinsic radiosensitivity of cancer cells is less clear, we have studied the impact of NF-kappaB on the intrinsic radiosensitivity of human cancer cells. METHODS We used PC3 prostate cancer cells and HD-MyZ Hodgkin's lymphoma cells transduced with an adenovirus vector that contains a gene encoding a form of IkappaB (an inhibitor of NF-kappaB) that cannot be phosphorylated. This form of IkappaB will remain bound to NF-kappaB; thus, NF-kappaB cannot be activated. We monitored NF-kappaB activity with a gel-shift assay and used a colony-forming assay to assess clonogenicity and radiosensitivity. RESULTS Constitutive DNA-binding activity of NF-kappaB was dramatically decreased in PC3 cells transduced with the IkappaB super-repressor gene. The clonogenicity of transduced PC3 cells declined to 19.6% of that observed for untreated control cells, a finding similar to one we have previously demonstrated for IkappaB-transduced HD-MyZ cells. However, inhibition of NF-kappaB activity in the surviving PC3 and HD-MyZ cells failed to alter their intrinsic radiosensitivity. CONCLUSIONS We conclude that activation of NF-kappaB does not determine the intrinsic radiosensitivity of cancer cells, at least for the cell lines tested in this study.
منابع مشابه
ANTISENSE RNA TO THE TYPE I INSULIN-LIKE GROWTH FACTOR RECEPTOR REVERSED THE TRANSFORMED PHENOTYPE OF PC-3 HUMAN PROSTATE CANCER CELL LINE IN VITRO
The insulin-like growth factor I receptor (IGF-IR) plays an essential role in the establishment and maintenance of transformed phenotype. Interference with the IGF-IR pathway by antisense causes reversal of the transformed phenotype in many rodent and human tumor cell lines. We stably transfected the PC-3 human prostate cancer cell line with an IGF-IR antisense RNA expression plasmid. The ...
متن کاملInhibition of constitutively activated nuclear factor-kappaB radiosensitizes human melanoma cells.
Melanoma tumors and cultured cell lines are relatively resistant to the cytotoxic effects of ionizing radiation, thereby limiting the use of radiotherapy for the clinical treatment of melanoma. New strategies for sensitizing melanoma cells therefore deserve examination. In an attempt to identify and target signaling pathways that contribute to radioresistance, we investigated the role of nuclea...
متن کاملVGB3 Induces Apoptosis by Inhibiting Phosphorylation of NF-κB p65 at Serine 536 in the Human Umbilical Vein Endothelial Cells
Background and objectives: Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibition results in an increase in apoptosis. It has been demonstrated that NF-κB subunit p65 phosphorylation at the IκB kinase phosphorylation site serine 536 (Ser536) is essential for the NF-κB nuclear translocation and activation. Therefore, NF-κB can be downregulated by suppressing its phosph...
متن کاملSynergistic activity of sorafenib and sulforaphane abolishes pancreatic cancer stem cell characteristics.
Recent evidence suggests that pancreatic cancer and other solid tumors contain a subset of tumorigenic cells capable of extensive self-renewal that contribute to metastasis and treatment resistance. Sorafenib (SO) is a promising new multikinase inhibitor for treatment of advanced kidney and liver cancers. We report here targeting of pancreatic cancer stem cells (CSC) by SO and the development o...
متن کاملConstitutive activation of NF-kappaB in human hepatocellular carcinoma: evidence of a cytoprotective role.
Activation of nuclear factor-kappaB (NF-kappaB) can promote or inhibit apoptosis. Oxidative stress is an important mechanism by which certain anticancer drugs kill cancer cells, and is also one of the mechanisms that activate NF-kappaB. We therefore examined hepatic expression of the NF-kappaB monomer p65 in human hepatocellular carcinoma (HCC) tissue samples from eight patients and compared it...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of the National Cancer Institute
دوره 91 22 شماره
صفحات -
تاریخ انتشار 1999