4 results about "Autophagic death" patented technology

The invention belongs to the technical field of biological medicine, discloses a novel venom polypeptide composite dendrimer as well as a preparation method and application thereof, and particularly discloses scorpion venom polypeptide, and the amino acid sequence of the scorpion venom polypeptide is FLGGSLSSIF. According to the invention, a novel scorpion venom polypeptide (marked as C9) is separated and identified, and a novel polypeptide-polyamidoamine dendritic compound G5C9 (i.e., nanoparticles) with a glioblastoma (GBM) targeting effect is constructed. Compared with the polypeptide C9, the cell uptake efficiency of the G5C9 is obviously improved. G5C9 can enter cells through endocytosis and target lysosome to destroy functions of the lysosome and mTORC1, so that nuclear translocation of TFEB is promoted, and autophagic death of the cells is induced. Therefore, the G5C9 provides a novel mode for targeting the anti-GBM in vitro and in vivo.

This invention belongs to the field of biomedical technology and provides the application of 16'-DEC in the preparation of anti-hepatocellular carcinoma drugs. This bisindole alkaloid compound can inhibit the proliferation and migration of hepatocellular carcinoma cells and can produce a synergistic anti-tumor effect with lenvatinib, solving the problems of limited efficacy and insufficient patient survival benefit of existing targeted drugs in hepatocellular carcinoma treatment. Experiments have confirmed that 16'-DEC exerts its anti-tumor effect by directly inhibiting mTOR kinase activity. This compound can specifically bind to mTOR protein, significantly upregulate the expression of autophagy-related genes by blocking the mTOR signaling pathway, and induce autophagic cell death in tumor cells. In vitro and in vivo experiments have demonstrated that inhibiting autophagy can reverse the anti-cancer effect of 16'-DEC, indicating that its pharmacodynamic mechanism mainly depends on the activation of the autophagy pathway. This invention is applicable to the development of novel targeted therapies for hepatocellular carcinoma, especially specific inhibitors of the mTOR signaling pathway.

The invention is applicable to the technical field of biological medicines, and provides application of targeted CHAF1B in preparation of a medicine for regulating and controlling autophagy activity of breast cancer cells. The invention reveals that targeted CHAF1B can activate autophagic death of breast cancer cells for the first time, provides a new strategy for molecular targeted therapy of breast cancer, and shows a good anti-tumor effect; the CHAF1B is proved to be remarkably and highly expressed in breast cancer tissues and is related to prognosis of patients, so that the CHAF1B can be used as a potential diagnosis, treatment and prognosis monitoring target of the breast cancer; the invention discusses that CHAF1B targeted MAPK signal channel induces autophagic death, provides theoretical support for application of CHAF1B as a new therapeutic target, enriches cognition of CHAF1B for regulating breast cancer cell proliferation molecular mechanism, provides a new thought and direction for searching for a new target for breast cancer treatment, and provides a new foundation for application of CHAF1B targeted MAPK signal channel induced autophagic death and application of CHAF1B targeted MAPK signal channel induced autophagic death. And a theoretical basis and an experimental basis are provided for clinically developing a new treatment target.

Provided are a new venom polypeptide-dendrimer complex, and a preparation method therefor and the use thereof. Specifically, provided is a scorpion venom polypeptide, wherein the amino acid sequence of the scorpion venom polypeptide is FLGGLLSSIF. A new scorpion venom polypeptide (designated as C9) is isolated and identified. Moreover, a new polypeptide-polyamidoamine dendrimer complex G5C9 (i.e., nanoparticles) having a glioblastoma (GBM)-targeting effect is constructed. Compared with polypeptide C9, G5C9 exhibits significantly improved cellular uptake efficiency. G5C9 can enter cells via endocytosis and targets lysosomes, and inhibits lysosomal function and mTORC1, thereby promoting nuclear translocation of TFEB and further inducing autophagic cell death. Therefore, G5C9 provides a new targeted anti-GBM approach both in vitro and in vivo.