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Ad-VT causes ovarian cancer A2780 cell death via mitochondrial apoptosis and autophagy pathways. | LitMetric

AI Article Synopsis

  • The study investigates the mechanism of a recombinant adenovirus, Ad-VT, which has a dual action against ovarian cancer cells, specifically targeting apoptosis and autophagy.
  • Using various laboratory techniques, the research demonstrates that Ad-VT significantly inhibits the growth of ovarian cancer cells while sparing normal cells, showing effective tumor suppression in an animal model.
  • The results indicate that Ad-VT primarily induces apoptosis through the endogenous pathway and enhances autophagy in cancer cells, which serves as a protective mechanism against cell death.

Article Abstract

Objective: The recombinant adenovirus Ad-apoptin-hTERTp-E1a (Ad-VT) to have a bi-specific oncolytic character in many tumor cells, but its action pathway in killing tumor cells has not been accurately elucidated. Here, we studied the mechanism of apoptosis and autophagy induced by Ad-VT and the interaction between autophagy and apoptosis.

Methods: Crystal Violet staining and CCK-8 assays were used to detect the inhibitory effect of Ad-VT on ovarian cancer cells. The antitumor effect of Ad-VT in vivo was analyzed by tumor bearing nude mouse model. Subsequently, flow cytometry and fluorescence staining were used to analyze the main types of apoptosis and autophagy induced by Ad-VT.

Results: In this study, through the in vitro cell inhibition assays, we found that Ad-VT has a significant inhibitory effect on ovarian cancer A2780 cells, but no significant inhibitory effect on normal ovarian epithelial cells. Then in vivo experiments showed that Ad-VT significantly inhibited tumor growth and extended the survival time of mice. Subsequent detection of the level of apoptosis found that Ad-VT can cause a strong apoptotic response and kill cells mainly through the endogenous apoptotic pathway. Through the staining analysis of LC3 and the analysis of autophagy-related proteins, it was found that Ad-VT could significantly increase the level of autophagy in A2780 cells, and this was a protective mechanism.

Conclusions: Ad-VT, which replicates under the control of the hTERT promoter and expresses apoptin protein, have significant inhibitory effect on ovarian cancer A2780 cells and promote their apoptosis and autophagy.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334942PMC
http://dx.doi.org/10.1016/j.tranon.2024.102067DOI Listing

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