[Synergistic lethal effect of mDRA-6 and nimesulide on human hepatocellular cancer cell line SMMC-7721]
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Ying-Jie Liu1, Yuan-Fang Ma, Jun Zhang
1Institute of Immunology, Key Laboratory of Cellular and Molecular Immunology, Henan University, Kaifeng, Henan, 475004, PR China.
Background & Objective:
Both mDRA-6, a monoclonal antibody of death receptor 5 (DR5) in human cells prepared by our key laboratory, and nimesulide, a specific cyclooxygenase-2 (COX-2) inhibitor, can induce apoptosis of some malignant tumor cells. This study was to investigate the lethal effects of mDRA-6 and nimesulide on human hepatocellular cancer cell line SMMC-7721, and explore the possible mechanism.
Methods:
The expression of DR5 on SMMC-7721 cells was detected by flow cytometry (FCM). SMMC-7721 cells were treated with mDRA-6 and nimesulide alone or in combination. Cell morphology was observed under microscope with Hoechst33258 staining. Cytotoxicity was examined by MTT assay. Cell apoptosis was detected by FCM.
Results:
The positive rate of DR5 on SMMC-7721 cells was 95.0%. The apoptosis of SMMC-7721 cells could be induced by both mDRA-6 and nimesulide: the apoptosis rates were 10.5% when treated with 25 ng/mL mDRA-6 for 12 h, 35.0% when treated with 1 600 ng/mL mDRA-6, 5.0% when treated with 200 micromol/L nimesulide, and 34.0% when treated with 800 micromol/L nimesulide. The combination of mDRA-6 and nimesulide exhibited synergistic effect on the apoptosis of SMMC-7721 cells (q=1.23): the apoptosis rates were 31.2% when treated with 200 micromol/L nimesulide and 25 ng/mL mDRA-6 for 12 h, and 91.1% when treated with 200 micromol/L nimesulide and 1 600 ng/mL mDRA-6 for 12 h.
Conclusions:
Both mDRA-6 and nimesulide can induce the apoptosis of SMMC-7721 cells. The combination of mDRA-6 and nimesulide exhibits synergistic lethal effect on SMMC-7721 cells.
Insights
The monoclonal antibody mDRA-6 and nimesulide synergistically induce apoptosis in hepatocellular cancer cells. This combination therapy significantly enhances cell death in SMMC-7721 cells, offering a promising strategy for cancer treatment.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Biology
Context:
- Hepatocellular carcinoma (HCC) remains a significant global health challenge with limited effective treatments.
- Death receptor 5 (DR5) agonists and cyclooxygenase-2 (COX-2) inhibitors are emerging as potential therapeutic agents for various cancers.
- Understanding the combined effects of these agents is crucial for developing novel HCC therapies.
Purpose:
- To investigate the synergistic lethal effects of mDRA-6, a monoclonal antibody targeting DR5, and nimesulide, a COX-2 inhibitor, on the human hepatocellular cancer cell line SMMC-7721.
- To explore the underlying mechanisms of cell death induced by the combination therapy.
- To evaluate the potential of this combination as a novel therapeutic strategy for HCC.
Summary:
- SMMC-7721 cells express high levels of DR5 (95.0%).
- Both mDRA-6 and nimesulide monotherapies induced significant apoptosis in SMMC-7721 cells.
- The combination of mDRA-6 and nimesulide demonstrated a synergistic effect, dramatically increasing apoptosis rates (up to 91.1%) compared to monotherapies.
Impact:
- This study highlights the potent synergistic anti-cancer activity of combining a DR5-targeting antibody with a COX-2 inhibitor in HCC.
- The findings suggest that this combination therapy could represent a promising new approach for treating hepatocellular carcinoma.
- Further research into the molecular mechanisms could pave the way for clinical translation and improved patient outcomes.
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