# Cyclin-dependent kinase inhibitor dinaciclib potently synergizes with cisplatin in preclinical models of ovarian cancer

## TL;DR

Dinaciclib, a CDK inhibitor, works well with cisplatin to fight ovarian cancer in preclinical models by boosting cell death and reducing tumor growth.

## Contribution

The study reveals that combining dinaciclib with cisplatin synergistically enhances anticancer effects in ovarian cancer models.

## Key findings

- Dinaciclib alone inhibits ovarian cancer cell growth and induces apoptosis.
- Combining dinaciclib with cisplatin synergistically promotes cell cycle arrest and tumor growth inhibition in mice.
- ROS levels increase with dinaciclib treatment, partially blocked by N-acety-L-cysteine.

## Abstract

Ovarian cancer is one of the most lethal of woman cancers, and its clinical therapeutic outcome currently is unsatisfied. Dinaciclib, a novel small molecule inhibitor of CDK1, CDK2, CDK5 and CDK9, is assessed in clinical trials for the treatment of several types of cancers. In this study, we investigated the anticancer effects and mechanisms of dinaciclib alone or combined with cisplatin in ovarian cancer. Dinaciclib alone actively induced cell growth inhibition, cell cycle arrest and apoptosis with the increased intracellular ROS levels, which were accompanied by obvious alterations of related proteins such as CDKs, Cyclins, Mcl-1, XIAP and survivin. Pretreatment with N-acety-L-cysteine significantly blocked ROS generation but only partially rescued apoptosis triggered by dinaciclib. Moreover, the combination of dinaciclib with cisplatin synergistically promoted cell cycle arrest and apoptosis, and inhibited the subcutaneous xenograft growth of ovarian cancer in nude mice. Altogether, dinaciclib potently synergizes with cisplatin in preclinical models of ovarian cancer, indicating this beneficial combinational therapy may be a promising strategy for treatment of ovarian cancer.