Cell proliferation and migration play important parts in ovarian cancer progression. BMP9, as one of the members of the TGF-ant array of biological roles, including cell differentiation, proliferation, apoptosis, tumorigenesis, and metabolism. However, the role and mechanism of BMP9 in ovarian cancer progression remains uncertain. We found that the expression of BMP9 was increased in human ovarian cancer cell lines, which induced Notch1 intracellular domain (NICD1) accumulation. And we also found the expression abundance of BMP9 is low in ovarian cancer cells. Thus, we generated recombinant adenoviruses overexpressing BMP9 to perform the research. We found that overexpression of BMP9 promoted ovarian cancer cell proliferative viability, cell cycle progression, cell migration in vitro, and accelerated subcutaneous tumor growth in vivo, which was inhibited by dominant-negative mutant Notch1 recombinant adenoviruses. Besides, we also demonstrated that silencing BMP9 by recombinant adenoviruses inhibited ovarian cancer cell viability and migration in vitro. Additionally, BMP9-induced ovarian cancer cell progression also involved the e levation of HES2, c-Myc, MMP9, and Cyclin D1, as well as repressed expression of p27. Together, these results revealed that BMP9 acts as a promoting factor in ovarian cancer progression, and overexpression of BMP9 promotes ovarian cancer progression and growth via Notch1 signaling.Thereby our research may provide new insight into the pathogenesis of ovarian cancer and BMP9-Notch1 signaling may serve as a novel therapeutic target axis for ovarian cancer treatment.

Alloimperatorin is a compound extracted from the traditional Chinese medicine (Angelica dahurica), which has exhibited anticancer activity. However, its precise molecular mechanism of anticancer remains unclear. Alloimperatorin-induced apoptosis of cervical cancer cells and its molecular mechanism were investigated in the present study. Cholecystokinin octapeptide (CCK-8) was employed to evaluate the cytotoxicity of alloimperatorin on HeLa, SiHa, and MS-751 cells. Flow cytometry was used to assess apoptosis induced by alloimperatorin. The mechanism of apoptosis was verified by mitochondrial membrane potential, Western blotting, and fluorescent PCR. The results of the study showed that alloimperatorin reduced the activity of HeLa cells. The calculated IC50 at 48 hours was 116.9 μM. Compared with the control group, alloimperatorin increased the apoptotic rate of HeLa cells and reduced the mitochondrial membrane potential of HeLa cells. The Western blot results showed that alloimperatorin promotes the expression of caspase3, 8, 9 and that Bax apoptotic proteins reduce PARP expression, procaspase3, 8, 9, and BCL-2 proteins and reduces the cyt-c in the mitochondria expression. The results demonstrated that alloimperatorin can induce HeLa cell apoptosis through mitochondria and extrinsic apoptotic pathways.

No abstract

No abstract