Apoptosis is a cell suicide program that includes a series of morphological and biochemical changes, and the pathogenesis of most diseases is related to apoptosis. The main ways of inducing apoptosis are endoplasmic reticulum pathway (such as the influence of Ca2+ channel), mitochondrial apoptosis pathway, death receptor pathway and other factors (such as the radiosensitivity of tumor cells).
1 Influence of Ca2+ channels
When Ca2+ is released from the endoplasmic reticulum into the cytoplasm, it will activate calpain near the endoplasmic reticulum, and then act on caspase-12 (caspases-12) to activate it and release it into the cytoplasm, thereby inducing apoptosis. Bee Venom Powder can increase the permeability of cell membranes to ions, especially Na+ and Ca2+. Ca2+ can carry signals to activate cells to perform their programmed functions.
The SARIS study found that calcium overload can induce apoptosis and is established by a variety of cells. CHU et al. found that melittin can induce Ca2+ influx through L-type Ca2+ channels in human osteoma cell MG63, which increases the intracellular Ca2+ concentration, leads to cell lysis and causes MG63 cell apoptosis, and Ca2+ influx is independent of protein kinases C and phospholipase A2 activity.
2 Mitochondrial apoptosis pathway
The active center of apoptosis regulation is mitochondria. Mitochondria release pro-apoptotic factors such as cytochrome C under the stimulation of apoptotic factors. In mitochondria, it promotes the release of cytochrome C. Bcl-2 family proteins can regulate the mitochondrial permeability transition pore, which in turn regulates the release of cytochrome C from mitochondria to the cytoplasm, and plays a key role in the regulation of apoptosis.
Li Yumei and others found that Bee Venom Powder can induce apoptosis of U2OS cells, and can promote the changes in the expression of anti-apoptotic proteins Bcl-2 and Bax proteins in U2OS cells, and the Bax/Bcl-2 ratio changes, first activate caspases-9, and then activate caspases-9. caspases-3, and finally induce apoptosis. After Zhang Chen treated BEL-7402 cells with different concentrations of melittin, the expression rate of mitochondrial membrane protein 7A6 increased, and the expression rate increased with the increase of melittin concentration, which had a promoting effect on the apoptosis of liver cancer cells .
3 Death receptor pathway
The pathway of death receptor-mediated apoptosis is mainly to transmit signals from extracellular to intracellular through transmembrane receptors. After the adaptor protein binds to the receptor, the executive protein binds to the adaptor protein to induce apoptosis. Its pathways mainly include activation-induced tumor necrosis factor receptor, tumor necrosis factor-related apoptosis-inducing ligand (TNF-related apoptosisinducing ligand, TRAIL) and FAS/FASL. After treating BEL-7402 cells with Bee Venom Powder, Zhang Chen found that melittin had an effect on Fas protein related to apoptosis according to the results of RT-PCR amplification. expression related.
Wang Chen and other scholars found that melittin can promote the sensitivity of human hepatoma cells to TRAIL by constructing a mouse tumor-bearing model, and it can promote the activation of calcium/calmodulin-dependent protein kinase II-transforming growth factor β-activated kinase 1-mitogen. Pro-activated protein kinase kinase-JNK/p38 signaling pathway and inhibition of nuclear factor κB inhibited protein kinase-nuclear factor κB signaling pathway synergistically TRAIL-induced apoptosis of human hepatoma cells.
4 Improve the radiosensitivity of tumor cells
Radiation therapy and chemotherapy are important means of treating tumors. Generally speaking, the effect of tumor radiotherapy is related to radiosensitivity, that is, the treatment effect of strong radiosensitivity is good, and the treatment effect of poor radiosensitivity is poor. Foreign scholars have found that Bee Venom Powder can enhance the radiosensitivity of esophageal cancer, resulting in enhanced apoptosis in vitro and in vivo. Scholars believe that melittin and radiation-induced apoptosis may be activated through the Bax/Bcl-2 pathway, and thus concluded that melittin-mediated radiosensitization may be partly due to the regulation of Bcl-2 protein.
Yang Xi received different doses of X-ray radiation on nasopharyngeal carcinoma CNE-2 cells, and found that both the normoxia group and the hypoxia group after combined melittin were significantly lower than the previous cell survival scores. The sensitization ratios of melittin in CNE-2 normoxic and hypoxic cells were 1.07 and 1.13, respectively, and melittin was able to increase the overall apoptosis rate of normoxic and hypoxic CNE-2 cells after irradiation. Therefore, melittin can effectively improve the radiosensitivity of tumor cells and promote the induction of apoptosis of tumor cells.