Antitumor effect of a dual cancer-specific oncolytic adenovirus on prostate cancer PC-3 cells

Abstract

Purpose: Apoptin can specifically kill cancer cells but has no toxicity to normal cells. Human telomerase reverse transcriptase (hTERT) acts as a tumor-specific promoter, triggering certain genes to replicate or express only in tumor cells, conferring specific replication and killing abilities. This study aimed to investigate the anticancer potential of the recombinant adenovirus Ad-apoptin-hTERTp-E1a (Ad-VT) in prostate cancer.

Methods: The pGL4.51 plasmid was used to transfect PC-3 cells to construct tumor cells stably expressing luciferase (PC-3-luc). Crystal violet staining and MTS assays determined the ability of Ad-VT to inhibit cell proliferation. Ad-VT-induced apoptosis of PC-3-luc cells was detected using Hoechst, Annexin V, JC-1 staining, and caspases activity analysis. PC-3-luc cells invasion and migration were detected using cell-scratch and Transwell assays. In vivo tumor inhibition was detected using imaging techniques.

Results: Crystal violet staining and MTS results showed that the proliferation ability of PC-3-luc cells decreased significantly. Hoechst, JC-1, and Annexin V experiments demonstrated that Ad-VT mainly induced apoptosis to inhibit PC-3-luc cell proliferation. Ad-VT could significantly inhibit the migration and invasion of PC-3-luc cells over a short period of time. In vivo, Ad-VT could effectively inhibit tumor growth and prolong survival of the mice.

Conclusions: The recombinant adenovirus, comprising the apoptin protein and the hTERTp promoter, was able to inhibit the growth of prostate cancer PC-3 cells and promote their apoptosis.

Keywords: Apoptin; PC-3-luc cells; Recombinant adenovirus; hTERT.