Volasertib suppresses tumor growth and potentiates the activity of cisplatin in cervical cancer

Am J Cancer Res. 2015 Nov 15;5(12):3548-59. eCollection 2015.

Abstract

Volasertib (BI 6727), a highly selective and potent inhibitor of PLK1, has shown broad antitumor activities in the preclinical and clinical studies for the treatment of several types of cancers. However, the anticancer effect of volasertib on cervical cancer cells is still unknown. In the present study, we show that volasertib can markedly induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the decreased protein expressions of PLK1 substrates survivin and wee1 in human cervical cancer cells. Furthermore, volasertib also enhances the intracellular reactive oxidative species (ROS) levels, and pretreated with ROS scavenger N-acety-L-cysteine totally blocks ROS generation but partly reverses volasertib-induced apoptosis. In addition, volasertib significantly potentiates the activity of cisplatin to inhibit the growth of cervical cancer in vitro and in vivo. In brief, volasertib suppresses tumor growth and potentiates the activity of cisplatin in cervical cancer, suggesting the combination of volasertib and cisplatin may be a promising strategy for the treatment of patients with cervical cancer.

Keywords: Volasertib; cervical cancer; cisplatin; combination therapy.