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Published on: January 19, 2019
Inhibition of human lung adenocarcinoma growth using survivint34a by low-dose systematic administration
Yan Shan1, Chunting Wang, Li Yang
1State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Chengdu, Sichuan, 610041, China.
Abstract:
Anti-apoptosis plays an important role in tumour formation and development. Survivin is a member of the inhibitor of apoptosis (IAP) family, which is a target for anti-cancer drug exploitation was replaced as development. We investigated the role of the homo dominant-negative mutant Survivin-T34A in suppressing human lung adenocarcinomas (A549). The anti-tumour activity of HSurvivinT34A plasmid was evaluated in the A549 cell line and nude mice bearing A549 subcutaneous tumours. Low-dose systemic administration was continuously used. The HSurvivinT34A plasmid (5 meu g/one) complexed with a cationic liposome (DOTAP/Chol) significantly inhibited tumour growth in our model. We observed microvessel density degradation by CD31 immunohistochemistry and apoptotic cell increase by TUNEL assay, PI staining and flow cytometric analysis in the treated group. The present findings suggest that the HSurvivinT34A plasmid complexed with a cationic liposome may provide an effective approach to inhibit the growth of human lung adenocarcinomas in vitro and in vivo.
Insights
A novel Survivin-T34A plasmid effectively suppressed human lung adenocarcinoma growth in vitro and in vivo. This therapy reduced tumor microvessels and increased cancer cell apoptosis, offering a promising anti-cancer strategy.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Anti-apoptosis mechanisms are crucial in tumor development.
- Survivin, an inhibitor of apoptosis protein (IAP) family member, is a validated anti-cancer target.
- The dominant-negative mutant Survivin-T34A offers potential for cancer therapy.
Purpose of the Study:
- To investigate the anti-tumor efficacy of the homo dominant-negative mutant Survivin-T34A plasmid in human lung adenocarcinoma (A549) cells and xenograft models.
- To evaluate the therapeutic potential of Survivin-T34A delivered via a cationic liposome (DOTAP/Chol).
Main Methods:
- A549 cells and nude mice bearing subcutaneous A549 tumors were used.
- Low-dose systemic administration of HSurvivinT34A plasmid complexed with DOTAP/Chol was employed.
- Tumor growth inhibition, microvessel density (CD31 immunohistochemistry), and apoptosis (TUNEL assay, PI staining, flow cytometry) were assessed.
Main Results:
- The HSurvivinT34A plasmid/DOTAP/Chol complex significantly inhibited A549 tumor growth.
- Treatment led to decreased microvessel density within tumors.
- Increased apoptotic cancer cells were observed in the treated group.
Conclusions:
- The HSurvivinT34A plasmid complexed with a cationic liposome demonstrates significant anti-tumor activity against human lung adenocarcinoma.
- This therapeutic approach effectively reduces tumor vascularization and promotes cancer cell apoptosis.
- Survivin-T34A plasmid offers a promising strategy for treating lung adenocarcinomas.
