Similar Datasets
Project description:Effect of ribociclib on breast cancer cells
| PRJNA755676 | ENA
Project description:We report transcriptional response to ribociclib treatment in resistant and sensitive CAMA-1 cells using RNA sequencing. Acquired ribociclib resistant cells were generated by treating CAMA-1 cells over a period of 5 month. Cells were then treated with ribociclib or DMSO control and processed for RNA sequencing.
2020-06-22 | GSE143944 | GEO
Project description:Breast cancer remains the most prevalent malignancy among women worldwide. Although ribociclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, has demonstrated significant antitumor activity in breast cancer therapy, its clinical application is limited by hematological toxicity, cardiotoxicity, and patient tolerance. In this study, we synthesized a novel ribociclib derivative, YW-LF, and systematically evaluated its antitumor activity and underlying mechanisms. Through a series of in vitro assays—including MTT, colony formation, EdU incorporation, transwell migration, and invasion experiments—as well as in vivo evaluation using a chick chorioallantoic membrane (CAM) model, we demonstrated that YW-LF significantly inhibited breast cancer cell proliferation, migration, and invasion, while effectively suppressing tumor growth and angiogenesis. Compared to the positive control ribociclib, YW-LF exhibited superior antitumor efficacy. Transcriptomic profiling revealed that YW-LF suppressed tumor progression by activating the p53 signaling pathway and apoptosis-related pathways. Western blot analysis further validated the dysregulation of key proteins, providing protein-level evidence for its mechanism of action. Additionally, machine learning-based bioinformatics analysis identified three core genes (ADRB1, ATOH8, and CCNE2) with potential clinical significance in breast cancer diagnosis and treatment. Immune infiltration analysis highlighted the strong correlation of these genes with specific immune cell subsets within the tumor microenvironment, underscoring their critical roles in modulating breast cancer immunobiology. Collectively, this study elucidates the therapeutic potential of YW-LF, a ribociclib derivative, in breast cancer treatment and delineates its multifaceted mechanisms, offering a promising strategy to overcome the limitations of current CDK4/6 inhibitors.
2025-04-11 | GSE294223 | GEO
Project description:Breast cancer remains the most prevalent malignancy among women globally, with its incidence continuing to rise and ranking as the leading cause of cancer-related mortality in females. Ribociclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, suppresses tumor cell proliferation by blocking the transition from the G1 to S phase. This study investigates the molecular mechanisms and therapeutic efficacy of RB-1 (7-cyclopentyl-N-ethyl-N-methyl-2-((3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide), a novel Ribociclib derivative, in inhibiting breast cancer progression. The effects of RB-1 on breast cancer cell viability were evaluated via MTT assay. In vitro and in vivo experiments demonstrated that RB-1 significantly inhibited cell proliferation, colony formation, and the proportion of EdU-positive cells in multiple breast cancer cell lines (e.g., MDA-MB-231 and SKBR3). The chicken chorioallantoic membrane (CAM) assay revealed that RB-1 treatment markedly suppressed tumor angiogenesis, outperforming Ribociclib. Mechanistic studies indicated that RB-1 regulates the p53 signaling pathway and cell cycle-related targets (e.g., E2F targets, mitotic spindle assembly), specifically inhibiting CDK4/6-mediated cell cycle progression. Furthermore, machine learning analysis identified Hyaluronan-Mediated Motility Receptor (HMMR) as a diagnostic and prognostic biomarker for breast cancer, with its expression significantly correlating with tumor-infiltrating immune cells. This study highlights the anti-cancer potential of RB-1 and elucidates its molecular mechanisms, offering a promising therapeutic candidate and novel targets for breast cancer treatment.
2025-04-12 | GSE294375 | GEO
Project description:Breast cancer persists as the most prevalent malignancy and principal contributor to cancer-associated mortality among women worldwide, exhibiting marked disease heterogeneity and therapeutic resistance. Consequently, the development of novel therapeutic agents remains imperative. Ribociclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, has emerged as a focus in adjuvant breast cancer research due to its mechanism of cell cycle arrest induction.Building upon this rationale, we designed and synthesized a novel ribociclib derivative RB-BC, systematically investigating its anti-neoplastic efficacy and molecular mechanisms in breast cancer through integrated in vitro and in vivo experimental systems. The compound's anti-proliferative effects were quantitatively assessed via MTT assays , EdU incorporation assays , and colony formation assays .Functional characterization through cell adhesion assays, scratch wound healing assays, and Transwell invasion assays demonstrated RB-BC’s dose-dependent suppression of tumor migration and invasion. Mechanistic analyses via RNA sequencing and Western blotting revealed that its anti-tumor activity primarily stems from p53 pathway activation, inducing caspase-3-mediated apoptosis in breast cancer cells. Machine learning algorithms identified p53-associated genetic signatures, and subsequent bioinformatics analyses elucidated their significant correlation with immune cell infiltration dynamics in the tumor microenvironment (TME).Moreover, RB-BC effectively suppressed tumor growth in vivo and significantly disrupted angiogenesis in the chick chorioallantoic membrane (CAM) assay. In summary, the ribociclib-derived compound RB-BC demonstrates compelling potential as a candidate therapeutic agent for breast cancer.
2025-04-15 | GSE294486 | GEO
Project description:Transcriptional profiling of ribociclib-treated sensitive and ribociclib resistant CAMA-1 cells
| PRJNA602306 | ENA
Project description:Ongoing studies suggest that letrozole (LTZ), a drug used in the treatment of breast cancer, can potentially be repurposed as a novel therapeutic for Glioblastoma (GBM). In a phase 0/1 trial in recurrent GBM patients we observed that LTZ permeates into the GBM tissue and triggers dose-dependent changes in the expression of genes regulating cell cycle (e.g. CDKN2A/N2B, CDK4). Based on these observations, we hypothesized that a combination of cyclin dependent kinase (CDK) 4/6 inhibitors with LTZ may result in synergistic anti-GBM activity. Therefore, we assessed the anti-tumor effects of LTZ in combination with ribociclib, a third-generation CDK4/6 inhibitor and the brain pharmacokinetics of ribociclib. Using cell viability and neurosphere growth assay against a panel of patient-derived GBM lines both compounds were found to be cytotoxic when used as single agents and were strongly synergistic when used in combination. We then assessed the DNA damaging effects (ɣH2AX induction), cell cycle arrest and the induction of apoptosis (Annexin V-FITC/PI) of both compounds as single agents and when used in combination. LTZ potentiated ribociclib-induced DNA damage and cell cycle arrest leading to apoptosis. Systemic and brain pharmacokinetics analysis of ribociclib in Sprague-Dawley (SD) rats by serial blood and brain extracellular fluid (ECF) sampling showed that ribociclib penetrates the blood-brain barrier with a partitioning coefficient (Kpu, u, brain) of about 10%. Overall, our studies suggest that a combination of ribociclib with LTZ is likely to be strongly synergistic against GBM at concentrations of the drugs that can be achieved in the brain
2025-09-05 | GSE301688 | GEO
Project description:Ribociclib derivative Rib-CA suppresses breast cancer progression by inducing p53-dependent apoptosis
| PRJNA1248440 | ENA
Project description:Ribociclib Derivative RB-BC Induces Apoptosis in Breast Cancer through p53 Pathway Activation
| PRJNA1250294 | ENA
Project description:GPAM is well characterized in triglyceride synthesis, but has never been implicated in cancer. Our study report a role for GPAM in cell migration. Gene expression changes after GPAM silencing was investigated to gain insight into possible mechanisms underlying GPAM's role in cell migration.
2017-06-10 | GSE99860 | GEO