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Published on: June 13, 2014
[Antitumor effect by combination of shRNA interfering plasmid targeting PKM2 with recombinant endostatin]
Jing-Zhi Mao1, Wen-Hao Guo, Hua-Shan Shi
1State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
Objective:
To investigate the enhancement effect of the combination of shRNA interfering plasmid targeting PKM2 with recombinant Endostatin in the treatment of lung cancer.
Methods:
Twenty five BABL/nu/nu mice bearing A549 lung cancer were divided into 5 groups (NS control, psh-Control, psh-PKM2 treated group, Endostar treated group, psh-PKM2+Endostar treated group) and treated with shRNA interfering plasmid targeting PKM2 and recombinant Endostatin respectively or in combination. The expression of PKM2 in A549 detected with immunofluorescent assay. The interference effect of psh-PKM2 was determined by Western blot. The tumor volume, microvessel density (MVD), apoptosis index (AI) and side effects were observed.
Results:
The combination treatment of RNA interfering plasmid targeting PKM2 with recombinant Endostatin inhibited tumor growth obviously (P < 0.05); The combination group revealed a decreased MVD and an increased AI (P < 0.05).
Conclusion:
The combination of shRNA interfering plasmid targeting PKM2 with recombinant Endostatin might enhance anti-tumor effect by increasing the apoptosis of the cancer cell.
Insights
Combining PKM2 shRNA with Endostatin effectively inhibits lung cancer growth. This combination therapy significantly reduces tumor volume and microvessel density while increasing cancer cell apoptosis.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Context:
- Lung cancer remains a leading cause of cancer-related mortality worldwide.
- Targeting key regulatory proteins like PKM2 offers potential therapeutic strategies.
- Recombinant Endostatin is an anti-angiogenic agent with demonstrated efficacy in preclinical models.
Purpose:
- To evaluate the synergistic anti-cancer effects of combining PKM2-targeting shRNA with recombinant Endostatin in a lung cancer model.
- To assess the impact of this combination therapy on tumor growth, microvessel density, and apoptosis.
Summary:
- Mice bearing A549 lung cancer xenografts were treated with PKM2 shRNA, Endostatin, or their combination.
- Immunofluorescence and Western blot confirmed PKM2 expression and shRNA interference efficacy.
- Combination therapy significantly inhibited tumor growth, reduced microvessel density (MVD), and increased apoptosis index (AI) compared to monotherapies.
Impact:
- This study demonstrates the enhanced anti-tumor efficacy of a combined therapeutic approach targeting PKM2 and angiogenesis in lung cancer.
- The findings suggest that this combination strategy may represent a promising new treatment option for lung cancer patients.
- Further clinical investigations are warranted to translate these preclinical findings into patient benefit.
