Anti-tumor effect of a dual cancer-specific recombinant adenovirus on ovarian cancer cells.

Abstract

BACKGROUND:

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 at investigating the anticancer potential of the recombinant adenovirus Ad-apoptin-hTERTp-E1a (Ad-VT) in ovarian cancer treatment.

METHODS:

Crystal Violet staining and WST-1 assays were used to analyze the inhibitory effect of Ad-VT on ovarian cancer SKOV3 and OVCAR-3 cells. Ad-VT-induced apoptosis of ovarian cancer cells, was detected using Hoechst, Annexin V-FITC/PI, JC-1 staining. Cell migration and invasion of ovarian cancer cells were detected using cell-scratch and Transwell assays. The pGL4.51 plasmid was used to transfect and to generate SKOV3-LUC cells, that stably express luciferase. The in vivo tumor inhibition effect of Ad-VT was subsequently confirmed using a tumor-bearing nude mouse model.

RESULTS:

Ad-VT had a strong apoptosis-inducing effect on SKOV3 and OVCAR-3 cells, that was mainly mediated through the mitochondrial apoptotic pathway. The Ad-VT could significantly increase the inhibition of ovarian cancer cell migration and invasion. The Ad-VT also can inhibit tumor growth and reduce toxicity in vivo.

CONCLUSIONS:

The recombinant adenovirus, comprising the apoptin protein and the hTERTp promoter, was able to inhibit the growth of ovarian cancer cells and promote their apoptosis.

• Authors: Yingli Cui, Yiquan Li, Shanzhi Li, Wenjie Li, Yilong Zhu, Jing Wang, Xing Liu, Ying Yue, Ningyi Jin, Xiao Li
• Journal: Experimental cell research (Exp Cell Res) Vol. 396 Issue 1 Pg. 112185 (11 01 2020) ISSN: 1090-2422 [Electronic] United States
• PMID: 32828827 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020. Published by Elsevier Inc.

Chemical References

• Viral Proteins

Topics

• Adenoviridae (genetics, metabolism)
• Animals
• Apoptosis (genetics)
• Carcinoma, Ovarian Epithelial (genetics, metabolism, mortality, virology)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Chicken anemia virus (genetics, metabolism)
• Female
• Gene Expression
• Genetic Vectors (chemistry, metabolism)
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Mitochondria (genetics, metabolism)
• Oncolytic Virotherapy (methods)
• Ovarian Neoplasms (genetics, metabolism, mortality, virology)
• Survival Analysis
• Transgenes
• Tumor Burden
• Viral Proteins (genetics, metabolism)
• Xenograft Model Antitumor Assays