1.1 Induction of tumor cell apoptosis
Apoptosis, also known as programmed cell death, is an active cell suicide behavior. Under normal circumstances, cell proliferation and apoptosis maintain a balance relationship. Once this balance relationship is disrupted, it may lead to tumorigenesis. Tumor cells can be induced to mutate and apoptosis by chemical drugs. Licochalcone A acts on human ovarian cancer OVCAR-3 and SK-OV-3 cells, can down-regulate Bid, Bcl-2, Bcl-xL and survivin protein levels, and up-regulate Bax protein levels; it can cause a decrease in mitochondrial membrane potential and promote Cytochrome C releases, activates Caspases (-8, -9, -3); promotes the cleavage of PARP-1; up-regulates the expression level of the tumor suppressor gene p53, thereby promoting apoptosis. Similar studies found that licochalcone A can induce the human breast cancer cell line MCF-7 cells and human promyelosomes by down-regulating the expression of the anti-apoptotic protein Bcl-2, reducing the Bcl-2/Bax ratio, and promoting the cleavage of PARP protein. The leukemia cell line HL-60 cells apoptosis; recent studies also show that licochalone A can induce the apoptosis of gastric cancer cells, the mechanism may be related to the cleavage of PARP protein, down-regulation of Caspase-3, Bcl-2 protein expression, and up-regulation of Bax protein expression related. In vivo experiments showed that licochalcone A could significantly inhibit tumorigenesis in BALB/c mice subcutaneously inoculated with colorectal cancer CT-26 cells. Immunohistochemical TUNEL staining found that with the increase of licochalcone A dose, the proportion of apoptotic cells increased. gradually increase.
1.2 Prevention of chemical carcinogenesis, inhibition of tumor invasion and metastasis
Metastasis of malignant tumor cells is one of the characteristics that distinguish them from normal cells, and is its own biological feature. Tumor metastasis is the main reason for endangering the life of the host and affecting the therapeutic effect. Licochalcone A has obvious preventive effect on the tumor induced by chemical drugs. C57BL/6 colon cancer mice induced by azomethane chemical method were orally administered 5, 15, 30 mg·kg-1 licochalone A, The incidence of tumor was significantly reduced and was dose-dependent. In addition, a study on the prevention of metastasis by licochalone A found that licochalone A could significantly improve the survival rate of nude mice injected with CT-26 cells in the spleen, and at the same time inhibit liver metastasis.
1.3 Induction of tumor cell differentiation
Malignant tumor cells are similar to undifferentiated embryonic cells in morphology and function, and have the characteristics of high division. Induction of differentiation refers to the reversal of the re-differentiation of malignant tumors towards normal maturation in the presence of a differentiation-inducing agent. At present, tumor induction and differentiation therapy is a new idea and new method for tumor treatment. In vitro studies of licorice chalcone A have shown that it has inhibitory effects on a variety of tumor cells. Glycochalcone A acts on human promyelocytic leukemia HL-60 cells, which can induce an increase in the expression of non-specific esterase (NSE). Blue tetrazolium (NBT) reducing ability has no effect, NSE is a marker of macrophage (monocyte) formation, and NBT reducing ability is a marker of granulocyte formation, it is speculated that licochalone induces HL-60 cells to monocytes Cells differentiate instead of granulocytes.
1.5 Inhibition of angiogenesis
Tumor growth and metastasis depend on angiogenesis. Studies have found that licochalone A can inhibit angiogenesis both in vitro and in vivo. In vitro studies have found that licochalone A can significantly inhibit the proliferation (20μmol·L-1), migration (5-20μmol·L-1) and lumen formation (10-20μmol·L-1) of human umbilical cord vascular endothelial cells (HUVECs). 1), and the growth of rat aortic ring microvessels (10～20μmol·L-1) in a dose-dependent manner. In vivo studies showed that licochalcone A significantly inhibited the growth of colorectal cancer CT-26 cells inoculated in BALB/c mice. With the increase of concentration, CD31 and Ki-67 positive cells in tumor tissue decreased, but the apoptosis rate increased significantly. Its anti-angiogenic mechanism may be related to down-regulating vascular endothelial growth factor receptor (VEGFR)-2 activation and blocking VEGF/VEGFR-2 signaling pathway.