PAX9 functions as a tumor suppressor gene for cervical cancer via modulating cell proliferation and apoptosis

Abstract

To investigate the effect of PAX9 on the progression of cervical cancer (CC). PAX9 expression was quantified in CC tissues and adjacent normal tissues, as well as human CC cell lines and human cervical epithelial cells (HCerEpiC). PAX9-overexpression lentiviral vectors were transfected into CC cell lines, followed by the measurement of proliferation and apoptosis and the quantification of apoptosis-related proteins. In vivo, mice were subcutaneously injected with CaSki cells transfected with PAX9-overexpression lentiviral vectors and control vectors. Then, the volume and weight of tumors were measured followed by hematoxylin and eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and immunohistochemistry. PAX9 expression in the CC tissues was lower than that in the adjacent normal tissues, which was correlated with the FIGO stage, tumor size, infiltration depth, parametrium invasion, lympho-vascular space invasion tumor-positive lymph nodes, and prognosis. Furthermore, PAX9 in CC cell lines was also lower than in HCerEpiC. PAX9 inhibits the CC cell proliferation and promotes the apoptosis, with the up-regulations of caspase-3, poly(ADP-ribose) polymerase (PARP), and Bax and the down-regulation of Bcl-2. In vivo experiments demonstrated that in the PAX9 group, the tumor weight and volume were lower than those in the vector group accompanying the decreased Ki-67, cleaved-caspase-3, and Bax expressions and the increased TUNEL and Bcl-2 expression. PAX9 was lowly expressed in the CC tissues and associated with the clinicopathological characteristics and prognosis. PAX9 could inhibit proliferation of CC cell lines and promote the apoptosis, thus suppressing the tumor growth in vivo, indicating its potential therapeutic role for CC treatment.