UNBS5162 inhibits SKOV3 ovarian cancer cell proliferation by regulating the PI3K/AKT signalling pathway

摘要

Ovarian cancer is the gynaecological malignancy with the highest mortality rate worldwide, and effective and safe therapeutic methods are limited. UNBS5162, a derivative of naphthalimide, has a clear inhibitory effect on the proliferation of various tumour cells in vitro and in vivo as a pan-antagonist of CXC chemokine ligand expression, but whether it serves a function in ovarian cancer remains unclear. The aim of the present study was to determine the effects of UNBS5162 on the proliferation, migration and invasion of ovarian cancer cells. The cell viability was detected using a Cell Counting Kit-8 (CCK-8) assay. The invasion and migration of SKOV3 cells were determined using Transwell assays. Cell apoptosis was determined using flow cytometry. The apoptosis-associated proteins and associated factors, such as phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signalling pathway members, were detected using western blot analysis. The CCK-8 assay revealed that SKOV3 cell viability was affected by UNBS5162 in a dose- and time-dependent manner. In Transwell assays, UNBS5162 inhibited cell invasion and migration. Furthermore, it was identified that UNBS5162 markedly increased the apoptosis rate of SKOV3 cells. Simultaneously, the expression of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) was decreased and the expression of the pro-apoptotic proteins active caspase-3 and Bcl-2-associated X protein were increased in SKOV3 cells treated with UNBS5162. In addition, the expression levels of phospho (p-)AKT/total AKT, p-mammalian target of rapamycin (mTOR)/total mTOR, p-p70 S6 kinase (p70S6K)/total p70S6K and cyclin D1 were decreased in the UNBS5162-treated group. The results of the present study indicated that UNBS5162 inhibits proliferation, migration and invasion, and induces apoptosis in ovarian cancer cells, which may be regulated by the PI3K/AKT signalling pathway. These results suggest that UNBS5162 may be a potential novel drug for clinical ovarian cancer treatment.