CFLAR expression

Importantly, KH-3 sensitized TNBC cells to doxorubicin-induced apoptosis. In summary, this study delineates cFLIP's role in mediating doxorubicin resistance and identifies HuR as a positive regulator of cFLIP, offering a novel therapeutic avenue against chemoresistance in TNBC by combining HuR inhibition with doxorubicin.

The JHDM KDM4C regulated cFLIP expression by binding to its promoter, and KDM4C knockdown sensitized PDAC cells to TRAIL-induced apoptosis. The present findings suggest that Gln-derived aKG production is required for KDM4C-mediated epigenetic regulation of cFLIP, which leads to resistance to TRAIL.

These results suggested that GSK3β/ITCH axis regulated the stability of c-FLIP and impacting on TRAIL-induced apoptosis. Taken together, our study revealed a GSK3β/ITCH/c-FLIP axis that counteracts TRAIL-induced apoptosis in human lung adenocarcinoma cells.

By contrast, N-acetylcysteine had no effect on dapagliflozin-induced apoptosis and downregulation of cFLIP and cFLIP expression. The present study also demonstrated that dapagliflozin had no effect on HK-2 normal human kidney cells. Taken together, the present study revealed that dapagliflozin induced apoptosis via the downregulation of cFLIP and an increase in cFLIP instability, suggesting that dapagliflozin may be a feasible drug candidate for the treatment of human renal cancer.

In vitro cytotoxicity against a breast cancer tumour cell line was not altered by c-FLIPp43 expression, but the expression of c-FLIPp43 in Her2-CAR T cells lowered interferon-γ secretion, without markedly affecting IL-2 levels, and c-FLIPp43-Her2-CAR T cells showed reduced anti-tumour activity in immunodeficient mice with breast cancer. The findings of this study provide a new understanding of the effects of controlling extrinsic apoptosis pathway suppression in CAR T cells, suggesting that c-FLIPp43 expression reduces anti-tumour immunity through the modulation of effector T cell pathways.

Of note, it was found by western blot analysis that Bcl-2 protein expression was downregulated by the decreased protein stability of Bcl-2 in pioglitazone-treated Caki cells. In conclusion, these findings indicated that pioglitazone-induced apoptosis is regulated through caspase-mediated degradation of FLIP and reduction of Bcl-2 protein stability, suggesting that pioglitazone is a feasible apoptotic agent that could be used in the treatment of human RC.

Moreover, co-culture of IL-1β-stimulated hUCMSCs with embelin-treated breast cancer cells could effectively induce apoptosis in breast cancer cells. The combined effects of embelin and IL-1β-stimulated hUCMSCs may provide a new therapeutic strategy for breast cancer therapy.

Combined treatment induced downregulation of c-FLIP expression transcriptionally, and ectopic expression of c-FLIP attenuated combined treatment-induced apoptotic cell death with mdivi-1 plus cisplatin. Collectively, our data provide evidence that mdivi-1 might be a cisplatin sensitizer.

BMSCs-EVs-carried miR-20a-3p targets c-FLIP and increases TRAIL levels in HCC cells, thus promoting TRAIL-related apoptosis.

Additionally, chidamide (2 µmol/l) downregulated c‑FLIPL, HDAC1 and HDAC3 expression, and increased receptor‑interacting protein kinase 3 expression and the phosphorylation of mixed lineage kinase domain‑like pseudokinase in Jurkat and HUT‑78 cells. The results obtained in the present study revealed that chidamide may induce necroptosis via regulation of c‑FLIPL expression when apoptosis is inhibited in Jurkat and HUT‑78 cells.

Intracranial delivery of the system could be utilized to induce apoptosis of tumor cells upon rapamycin treatment. Our results demonstrate a novel inducible Fas activation system which operates with high efficiency and temporal precision in vitro and in vivo promising a potential therapeutic strategy.