ABSTRACT
Objective:To investigate the effects of anemoside B4 on proliferation, apoptosis and migration of ovarian cancer SKOV3 cells through a variety of biological methods, and further to explore its mechanism.Methods:Ovarian cancer SKOV3 cells were cultured in vitro. CCK-8 method was used to detect the proliferation of SKOV3 cells treated with different concentrations of anemoside B4, and IC50 value was calculated. Flow cytometry was employed to detect the apoptosis of cells treated with IC50 concentration of anemoside B4 for different time length; Transwell method was used to detect the migration and invasion of cells treated with IC50 concentration of anemoside B4 for different time length. Western blot was used to detect changes in the expression of related proteins.Results:Anemoside B4 can effectively inhibit the proliferation of SKOV3 cells, showing a concentration-dependent IC50 value of 6.08±0.56 μM, and the inhibitory effect is stronger than the positive control drug cisplatin, with statistically significant difference (P<0.05) . Flow cytometry showed that anemoside B4 could induce SKOV3 cells apoptosis, reduce Bcl-xl expression, and up-regulate the expression of Bax, cleaved-caspase-3 and PARP. Compared with the group of 0 h, the difference was statistically significant (P<0.05) . Crocetin could down-regulate the expression of N-cadherin and up-regulate the expression of E-cadherin, thereby inhibiting the migration of SKOV3 cells. Anemoside B4 could inhibit the expression of JAK/STAT3 signaling pathway proteins.Conclusion:Anemoside B4 can effectively inhibit the proliferation of cervical cancer cells, and induce SKOV3 cell apoptosis by regulating the JAK/STAT3 signaling pathway to inhibit their migration. Crocetin has great potential in the research and development of ovarian cancer therapy.
ABSTRACT
Signal transducer and activator of transcription 3 (STAT3) is an important regulatory factor of cell proliferation and metastasis, involved in the occurrence and development of a variety of malignant tumors, and it is one of the hot spots in the research of targeted anti-tumor drugs. Our group screened a novel benzobis (imidazole) structure small molecule compound LZJ541 through the screening model of Janus kinase (JAK)/STAT3 pathway inhibitors, which has definite STAT3 inhibitory activity. We examined the effect of LZJ541 on the proliferation of HepG2 and PC-3 cells by MTT assay in vitro, detected the effect of LZJ541 on the expression of STAT3-related proteins in HepG2 cells by Western blot, and measured the effect of LZJ541 on the apoptosis and cell cycle arrest of HepG2 cells via flow cytometry. The results indicated that LZJ541 significantly inhibited the activation of STAT3 signaling pathway and restrained the proliferation of HepG2 cells. Its half maximal inhibitory concentration (IC50) was 13.8 μmol·L-1, which was much lower than that of PC-3 cells (with low STAT3 expression, IC50: 41.99 μmol·L-1), LZJ541 can also inhibit the phosphorylation of STAT3 in HepG2 cells, thereby inducing apoptosis and cycle arrest and then exerting anti-tumor effects. In conclusion, LZJ541 has a certain anti-tumor effect in vitro, which provides an experimental basis for the development of new STAT3-targeted anti-tumor drugs around this kind of compounds.
ABSTRACT
Objective: To determine the effects of interleukin 2 (IL-2) on epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) synthesis in retinal pigment epithelial (RPE) cells. Methods: IL-2 of 10 μg/L was used to induce RPE cells. Real-time PCR and Western blot methods were used to detect the EMT marker α-smooth muscle actin (α-SMA), the extracellular matrix (ECM) markers fibronectin (Fn) and type I collagen (COL-1), transforming growth factor β2 (TGF-β2), and the activation of the JAK/STAT3 signaling pathway at corresponding time points. Furthermore, JAK/STAT3 signaling pathway was specifically blocked by WP1066, and the changes in α-SMA, COL-1, Fn and TGF-β2 mRNA and protein expressions were detected. Results: After induction by 10 μg/L of IL-2, the expressions of Fn, COL-1, TGF-β2 mRNA and protein as well as p-STAT3/STAT3 were significantly increased (P<0.05). This effect was correlated with the length of IL-2 treatment, while α-SMA mRNA and protein expression did not change significantly. JAK/STAT3 inhibitor WP1066 could effectively inhibit the expressions of Fn, COL-1 and TGF-β2 in IL-2-induced RPE cells. Conclusion: IL-2 promotes ECM synthesis and TGF-β2 expression in RPE cells via JAK/STAT3 signaling pathway, which may play an important role in proliferative vitreoretinopathy.
ABSTRACT
JAK/STAT3 signal pathway is an important intracellular signal transduction pathway. It plays important roles in cell apoptosis and proliferation by affecting the activity of downstream effector molecules,and also induces embryonic development,liver regeneration,glycolysis and inflammation,epithelial-mesenchymal transition and an-giogenesis and a series of biogenesis process,closely related to the development of human cancer.
ABSTRACT
JAK/STAT3 signal pathway is an important intracellular signal transduction pathway. It plays important roles in cell apoptosis and proliferation by affecting the activity of downstream effector molecules,and also induces embryonic development,liver regeneration,glycolysis and inflammation,epithelial-mesenchymal transition and an-giogenesis and a series of biogenesis process,closely related to the development of human cancer.
ABSTRACT
JAK/STAT3 signaling pathway exists in various organs and tissues and mediates multiple biological processes including cell proliferation,differentiation,migration,apoptosis and immunoregulation.Recently,it has been revealed that this pathway plays an important role in gastrointestinal diseases,promoting tumor growth,angiogenesis and inhibiting apoptosis in gastric and colorectal cancers,and being implicated in the pathogenesis of inflammatory bowel disease.Inhibitors targeting JAK/STAT3 pathway showed promising outcome in some disease models.In this review article,the advances in study of abovementioned issues were summarized.