TRIM28 knockdown increases sensitivity to etoposide by upregulating E2F1 in non-small cell lung cancer.

Tripartite motif containing 28 (TRIM28) is a universal corepressor for Kruppel-associated box zinc finger proteins. In our previous study, it was shown that expression of TRIM28 is upregulated in non-small cell lung cancer (NSCLC) cell lines and tissues. Here, we demonstrated that the stable silencing of TRIM28 expression by a specific siRNA lentivirus vector increased the sensitivity of NSCLC cells to chemotherapeutic agent etoposide. Combination of TRIM28 siRNA and etoposide significantly inhibited the growth and proliferation of lung adenocarcinoma PAa cells and exerted obvious antitumor effects in nude mice. Using FCM and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) assay, we found that TRIM28 siRNA in combination with etoposide increased apoptosis in vitro and in vivo which was induced by E2F1 activity, since the expression of E2F1 and its target genes was significantly increased in the cotreatment group. Cell proliferation and apoptosis were almost completely abolished in the PAa cells cotreated with TRIM28 siRNA and etoposide following knockdown of E2F1. The results of our study demonstrated that the combination of TRIM28 siRNA and etoposide may be effective against NSCLC and has the potential of being a new therapeutic tool for future treatment.