simvastatin

P2, N=184, Not yet recruiting, McGill University Health Centre/Research Institute of the McGill University Health Centre

The optimized nanoformulation (NP-PTX/SIM) exhibited significant synergistic anti-proliferative cytotoxic effects against HCT-116 cells (IC50 = 10.21 µg mL-1) compared to free drugs through caspase-3 activation and suppression of proliferative (Ki-67) and angiogenic vascular endothelial growth factor (VEGF) markers confirming its apoptotic effects. By integrating the established Eudragit S100-chitosan carrier with the novel co-delivery of pentoxifylline and simvastatin, coupled with QbD optimization and comprehensive therapeutic evaluation, this work presents a distinct and innovative multi-targeted therapeutic strategy for CRC with improved efficacy and reduced off-target effects.

GSDMD activation, often through NLRP3 inflammasome signaling or chemotherapeutic agents like simvastatin, induces pyroptosis and modulates immune infiltration...Harnessing its antitumor potential while mitigating pro-tumorigenic inflammation requires innovative strategies. Future research should focus on elucidating the isoform-specific roles of gasdermins, optimizing therapeutic approaches to induce pyroptosis.

Additionally, SIM significantly attenuated the overexpression of Cx43 and its phosphorylated form (pS368Cx43), which are responsible for impairing intercellular communication and electrical coupling in cardiomyocytes and contribute to arrhythmias and conduction abnormalities characteristic of acute Doxo-induced cardiotoxicity. Overall, these findings demonstrate that SIM exerts a multifaceted cardioprotective effect against Doxo-induced injury, thereby targeting interconnected inflammatory and pro-arrhythmic pathways implicated in Doxo cardiotoxicity.

Model cells were treated with ginsenoside F1 (0.2 µM, 0.8 µM, and 3.2 µM) or simvastatin (3.2 µM, positive control) for 24 h. Intracellular lipid accumulation was determined by measuring absorbance at 510 nm, together with quantification of total cholesterol (TC) and triglyceride (TG) contents...Potential roles of targets including Akt1, PPARG, and EGFR, as well as pathways related to cancer and lipid metabolism, were further indicated by network pharmacology and molecular docking. FFA-induced lipid disorders in HepG2 cells were alleviated by ginsenoside F1, potentially through the regulation of glycerophospholipid metabolism.

Our results have important clinical implications, as they emphasize the potential of targeting key lipid metabolic pathways to overcome the adaptive mechanisms associated with normoxic HIF-1α expression. Thus, our data offer promise for novel combination therapies which disrupt the metabolic plasticity of melanoma, to ultimately improve therapeutic outcomes.

Papain remains inactive during systemic circulation and intracellular trafficking, ensuring biosafety, but is selectively activated by tumor-released glutathione and boosted by localized photothermal heating to precisely degrade ECM, suppressing integrin signaling and PD-L1 transcription, while simvastatin-driven cholesterol depletion amplifies this effect by destabilizing integrin clusters and promoting PD-L1 degradation. Combined with phototherapy-induced immunogenic cell death, this strategy remodels ECM, enhances T cell infiltration, overcomes checkpoint blockade resistance, and eradicates advanced tumors (∼500 mm3).

P=N/A, N=781430, Active, not recruiting, Brigham and Women's Hospital | Trial completion date: Jul 2026 --> Sep 2027 | Trial primary completion date: Jan 2026 --> May 2026

In cervical cancer cisplatin-resistant cell lines (SiHa-DDP and C33a-DDP) constructed from their parental cells, the effects of seven statins (simvastatin, fluvastatin, pitavastatin, lovastatin, atorvastatin, rosuvastatin, and pravastatin) on cell viability in cisplatin-resistant cells and corresponding parental cells were assessed using the CCK-8 assay...In all, simvastatin enhanced cisplatin sensitivity by suppressing the CAV1-mediated PI3K/AKT pathway involvement in the development of cisplatin resistance in cervical cancer cells. These findings reveal a novel mechanism in cervical cancer cells resistant to cisplatin by which simvastatin may serve as a potential adjuvant to improve the therapeutic efficacy of cisplatin-based chemotherapy.

Curcumin did not sensitize HepG2-DR cells to doxorubicin, whereas verapamil and simvastatin enhanced doxorubicin cytotoxicity only at toxic concentrations. In contrast, several TKIs, including nilotinib, tivozanib, and, to a lesser extent, cabozantinib, exhibited synergistic effects with doxorubicin in HepG2-DR cells...Third-generation MDR1 inhibitors (tariquidar, elacridar, and zosuquidar) sensitized HepG2-DR and HB-303 cells at non-toxic nanomolar concentrations in vitro...MDR1 inhibitors, such as zosuquidar, may enable dose reductions of chemotherapeutic agents, whereas the use of synergistic TKIs, such as tivozanib, may improve therapeutic outcomes and minimize adverse effects in children with HB. TG100-115, a TRPM7 kinase inhibitor, provides neuroprotection and attenuates NLRP3 inflammasome-mediated neuroinflammation in a neonatal mouse model of hypoxic-ischemic brain injury.

P=N/A, N=12, Dermatology Hospital of Southern Medical University; Dermatology Hospital of Southern Medical University

P2, N=84, Recruiting, National Cancer Institute, Naples