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[Study on enhancing sensitivity of SPC-A1 cells to chemotherapy by Livin isoform-specific gene silencing]
Jianguo Sun1, Rongxia Liao, Zhengtang Chen
1Cancer Institute of PLA,Xinqiao Hospital,Third Military Medical University,Chongqing 400037,P.R.China.
Background:
As a new member of inhibitor of apoptosis protein(IAP) family,Livin,especially Livin α,is known to be involved in occurrence and development of lung cancer.Livin is an important mechanism of chemotherapy resistance of lung cancer cell.The aim of this study is to set up Livin isoform(α & β)-specific gene silencing system in SPC-A1 cells by gene transfection and RNA interference(RNAi),and to explore the different functions and value of the isoforms in enhancing chemosensitivity of SPC-A1 cells.
Methods:
Livinα+β,Livinα and Livinβ specific siRNA were expressed stably in SPC-A1 cells,respectively.MTT was performed to study sensitivity of the cells to chemotherapy drugs.In vivo experiment was performed to test sensitivity of mouse bearing tumor to cisplatin after gene silencing of Livin.
Results:
After silencing of Livinα+β,Livinα and Livinβ genes,sensitivity of SPC-A1 cells to many chemotherapy drugs(including cisplatin,carboplatin,cyclophosphamide and adriblastine) was markedly increased(P < 0.05).Among them,gene silencing of Livinα+β showed the strongest enhancement effect on chemosensitivity of SPC-A1 cells(P < 0.01).Animal experiment showed that tumor inhibition rate of pSilencer-Livinα+β,pSilencer-Livinα and pSilencer-Livinβ groups was 146.1%,130.7% and 110.5%,respectively.
Conclusions:
The results suggest that Livin isoform,especially Livinα+β is hopeful to be a molecular target for increasing sensitivity of lung cancer cell to chemotherapy.Gene silencing may be a new means of gene therapy for non-small cell lung cancer.
Insights
Silencing Livin isoforms, particularly Livin α+β, significantly enhances lung cancer cell sensitivity to chemotherapy drugs. This suggests Livin isoforms are potential molecular targets for improving lung cancer treatment outcomes.
Area of Science:
- Molecular Biology
- Oncology
- Gene Therapy
Context:
- Livin, an inhibitor of apoptosis protein (IAP) family member, is implicated in lung cancer development and chemotherapy resistance.
- Livin exhibits different isoforms, including Livin α and Livin β, which may have distinct roles in cancer progression.
Purpose:
- To establish a Livin isoform-specific gene silencing system in SPC-A1 lung cancer cells using RNA interference (RNAi).
- To investigate the functional roles of Livin isoforms (α and β) in modulating the chemosensitivity of lung cancer cells.
Summary:
- Stable expression of Livin α+β, Livin α, and Livin β specific small interfering RNAs (siRNAs) was achieved in SPC-A1 cells.
- Gene silencing of Livin isoforms markedly increased SPC-A1 cell sensitivity to various chemotherapy drugs, with Livin α+β silencing showing the most pronounced effect.
- In vivo studies demonstrated significant tumor inhibition rates in mice bearing tumors with silenced Livin isoforms, particularly Livin α+β.
Impact:
- Livin isoforms, especially Livin α+β, represent promising molecular targets for overcoming chemotherapy resistance in lung cancer.
- Gene silencing targeting Livin offers a potential novel gene therapy strategy for non-small cell lung cancer.
