Potentiation of tumor radiotherapy by a radiation‐inducible oncolytic and oncoapoptotic adenovirus in cervical cancer xenografts

Abstract

The p53 tumor suppressor pathway is impaired in more than 90% of cervical cancers and cancer-derived cell lines as a result of infection by human papillomavirus (HPV). The HPV E6 oncoprotein forms complexes with p53 and promotes its degradation via ubiquitin-dependent mechanism. In our study, we attempted to improve the clinical outcomes of this combined therapy by modifying the p53-targeted adenovirus to become radiation-responsive. The antitumor adenovirus was constructed by inserting a radiation-responsive expression cassette composed of the promoter of early growth response-1 (Egr-1) and the proapoptotic protein TRAIL. We showed that the addition of adenovirus containing Egr-1/TRAIL significantly increased cell death and apoptosis caused by radiotherapy. In mice bearing xenograft tumors, intratumoral administration of the Egr-1/TRAIL adenovirus followed by radiation significantly reduced tumor growth and enhanced tumor survival. Our Egr-1/TRAIL adenoviral gene product may offer a novel ''one-two punch'' tumor therapy for cervical cancers not only by potentiating radiation treatment but also by preserving p53 defect-specific tumor killing of the oncolytic adenovirus.

Egr1 mediates retinal vascular dysfunction in diabetes mellitus via promoting p53 transcription

“…5 What is more, Das et al held that Egr1 may regulate the transcription and expression of p53. 23 However, there was no information about the regulatory relationships between Egr1 and p53 in the DR Here, we observed that Egr1 showed an interaction with p53 and contributed to its transcriptional activity in HRVECs. 23 However, there was no information about the regulatory relationships between Egr1 and p53 in the DR Here, we observed that Egr1 showed an interaction with p53 and contributed to its transcriptional activity in HRVECs.…”

Epigenetic reprogramming reverses the malignant epigenotype of the MMP/TIMP axis genes in tumor cells

“…Cell growth curves were determined by MTT as described previously . Cells were seeded in the 96‐well plate (500 cells per well).…”

Histone deacetylase inhibitor valproic acid promotes the induction of pluripotency in mouse fibroblasts by suppressing reprogramming-induced senescence stress

“…Cell survival was measured using the MTT (3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide) assay [38,39]. Cells (1 Â 10 4 /well) were plated onto 96-well plates.…”