Anticancer and radiosensitizing effects of the cyclin-dependent kinase inhibitors, AT7519 and SNS-032, on cervical cancer

Cyclin-dependent kinases (CDK) are considered to be potential targets of anticancer drugs that can interrupt the uncontrolled division of cancer cells. In this study, we selected two selective CDK inhibitors, AT7519 and SNS-032, from current clinical trials and examined their anticancer and radiosensitizing effects in a cervical cancer model. SNS-032 was found to be more potent than AT7519, with a lower half maximal inhibitory concentration (IC50) value. Both AT7519 and SNS-032 induced the apoptosis, premature senescence and cytostasis of cervical cancer cells, which led to the attenuation of tumor growth in vivo. Moreover, using these CDK inhibitors together with radiation synergistically inhibited tumor growth in a human xenograft tumor model. The concomitant activation of the p53 tumor suppressor and the suppression of cell cycle checkpoint responses mediated by Chk1 led to the cytostasis of cervical cancer cells. Finally, AT7519 and SNS-032 inhibited cancer cell migration, invasion and angiogenesis in vitro, and suppressed lung metastases in a spontaneous metastasis model. On the whole, the findings of this study indicate that the utilization of AT7519 and SNS-032 as part of an adjuvant treatment may help control cervical cancer progression.