nutlin-3a has been researched along with Adenocarcinoma-of-Lung* in 2 studies
2 other study(ies) available for nutlin-3a and Adenocarcinoma-of-Lung
| Article | Year |
|---|---|
Combinatory inhibition of TRIM65 and MDM2 in lung cancer cells.
In addition to the involvement in white matter lesion, tripartite-motif protein family member 65 (TRIM65) has also been implicated in tumorigenesis as a potential oncogene. However, the underlining mechanisms of TRIM65 functions and its clinical implication still remain to be further elucidated. In the present study, we found that TRIM65 binds to the N-terminus of p53 tumor suppressor and thus competes with MDM2 for p53 binding. Intriguingly, analysis of the Cancer Genome Atlas (TCGA) gene alteration database revealed that elevated expression of TRIM65 is mutually exclusive to MDM2 up-regulation in human lung adenocarcinoma patients, indicating potential compensatory effect of one over the other. Indeed, overexpression of TRIM65 renders lung cancer cell line resistance to Nutlin-3a, an effective MDM2 inhibitor, as determined by p53 activation and cell proliferation assays. Furthermore, depletion of TRIM65 using siRNA in combination with Nutlin-3a treatment demonstrates enhanced anti-tumor effects on lung cancer cell line. Collectively, our findings provide the rationale for developing strategies to target TRIM65 for lung cancer intervention, potentially in combination with MDM2 inhibition. Topics: Adenocarcinoma of Lung; Binding, Competitive; Cell Line, Tumor; Cell Survival; Drug Resistance, Neoplasm; Drug Synergism; Humans; Imidazoles; Lung Neoplasms; Piperazines; Protein Binding; Proto-Oncogene Proteins c-mdm2; Tripartite Motif Proteins; Tumor Suppressor Protein p53; Ubiquitin-Protein Ligases | 2018 |
Lung tumors with distinct p53 mutations respond similarly to p53 targeted therapy but exhibit genotype-specific statin sensitivity.
Lung adenocarcinoma accounts for ∼40% of lung cancers, the leading cause of cancer-related death worldwide, and current therapies provide only limited survival benefit. Approximately half of lung adenocarcinomas harbor mutations in Topics: Adenocarcinoma; Adenocarcinoma of Lung; Animals; Antineoplastic Agents; Cell Cycle Checkpoints; Cell Death; Cell Line, Tumor; Disease Models, Animal; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Genotype; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Imidazoles; Lung Neoplasms; Mice; Molecular Targeted Therapy; Mutation; Piperazines; Simvastatin; Tumor Suppressor Protein p53 | 2017 |