Ad-VT causes ovarian cancer A2780 cell death via mitochondrial apoptosis and autophagy pathways
Yingli Cui1, Xin Chen2, Wenjie Li3
1Department of Gynecologic Oncology, First Hospital of Jilin University, Changchun 130021, PR China.
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.
Insights
Recombinant adenovirus Ad-apoptin-hTERTp-E1a (Ad-VT) effectively inhibits ovarian cancer cells by inducing apoptosis and autophagy. This oncolytic virus shows significant antitumor effects in vivo, offering a promising therapeutic strategy.
Area of Science:
- Oncolytic virology
- Cancer biology
- Molecular oncology
Background:
- Recombinant adenovirus Ad-apoptin-hTERTp-E1a (Ad-VT) exhibits bi-specific oncolytic activity.
- The precise mechanisms of Ad-VT-induced tumor cell death remain incompletely understood.
- Investigating the interplay between apoptosis and autophagy in Ad-VT's action is crucial.
Purpose of the Study:
- To elucidate the apoptosis and autophagy mechanisms induced by Ad-VT in ovarian cancer cells.
- To explore the interaction between autophagy and apoptosis pathways during Ad-VT treatment.
- To evaluate the therapeutic potential of Ad-VT against ovarian cancer.
Main Methods:
- In vitro assays (Crystal Violet staining, CCK-8) assessed Ad-VT's effect on ovarian cancer cells.
- In vivo studies utilized a tumor-bearing nude mouse model to evaluate antitumor efficacy.
- Flow cytometry and fluorescence staining (LC3) analyzed apoptosis and autophagy levels.
Main Results:
- Ad-VT demonstrated significant inhibition of ovarian cancer A2780 cells with minimal impact on normal cells.
- In vivo experiments confirmed Ad-VT's tumor growth inhibition and survival extension in mice.
- Ad-VT induced significant apoptosis via the endogenous pathway and increased protective autophagy in cancer cells.
Conclusions:
- Ad-VT effectively targets and inhibits ovarian cancer A2780 cells.
- The virus promotes both apoptosis and autophagy, contributing to its oncolytic effect.
- Ad-VT represents a potential therapeutic agent for ovarian cancer treatment.
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