TAPI-1 Exhibits Anti-tumor Efficacy in Human Esophageal Squamous Cell Carcinoma Cells via Suppression of NF-κB
Lin Gao1, Li Li2, Dongmei Zhang1
1Medical Research Center, Affiliated Hospital 2 of Nantong University and First People's Hospital of Nantong City, Nantong, 226001, People's Republic of China.
Background:
TNF-α processing inhibitor-1 (TAPI-1) is a known metalloproteinase inhibitor with potential anti-inflammatory effects. However, its anti-cancer effects on esophageal squamous cell carcinoma (ESCC) have not been uncovered.
Aim:
In the present study, the effects of TAPI-1 on ESCC cell viability, migration, invasion, and cisplatin resistance and the underlying molecular mechanisms were investigated in TE-1 and Eca109 cells.
Methods:
To this end, TE-1 and Eca109 cells were exposed to TAPI-1 for indicated time intervals. Cell viability was assessed using cell counting kit-8 assay and apoptosis was evaluated using flow cytometry assay. Migration and invasion were assessed using Transwell assays. Gene expressions were analyzed using quantitative reverse transcription polymerase chain reaction. The activation of NF-κB signaling pathway was elucidated via Western blot and chromatin immunoprecipitation assay.
Results:
We observed that higher doses (10, 20 μM) of TAPI-1 inhibited ESCC cell viability, while a lower dose (5 μM) of TAPI-1 inhibited ESCC cell migration and invasion and enhanced the chemosensitivity of ESCC cells to cisplatin. Moreover, TAPI-1 suppressed the activation of NF-κB signaling and the target genes expression in the stage of transcription initiation. Furthermore, blocking NF-κB signaling in advance could abolish all the effects of TAPI-1 on ESCC cells.
Conclusion:
Overall, these results indicated that TAPI-1 impairs ESCC cell viability, migration, and invasion and facilitates cisplatin-induced apoptosis via suppression of NF-κB signaling pathway. TAPI-1 may serve as a potential adjuvant agent with cisplatin for ESCC therapy.
Insights
TNF-α processing inhibitor-1 (TAPI-1) effectively inhibits esophageal squamous cell carcinoma (ESCC) growth and metastasis by suppressing NF-κB signaling. TAPI-1 also enhances cisplatin sensitivity, suggesting its potential as an adjuvant cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- TNF-α processing inhibitor-1 (TAPI-1) is a known metalloproteinase inhibitor with potential anti-inflammatory properties.
- The anti-cancer effects of TAPI-1 on esophageal squamous cell carcinoma (ESCC) remain largely uninvestigated.
Purpose of the Study:
- To investigate the effects of TAPI-1 on ESCC cell viability, migration, invasion, and cisplatin resistance.
- To elucidate the underlying molecular mechanisms, particularly the role of the NF-κB signaling pathway.
Main Methods:
- Exposure of TE-1 and Eca109 ESCC cells to varying doses of TAPI-1.
- Assessment of cell viability (CCK-8 assay), apoptosis (flow cytometry), migration, and invasion (Transwell assays).
- Analysis of gene expression (qRT-PCR) and NF-κB signaling pathway activation (Western blot, ChIP assay).
Main Results:
- TAPI-1 inhibited ESCC cell viability at higher doses (10, 20 μM) and suppressed migration and invasion at lower doses (5 μM).
- TAPI-1 enhanced the chemosensitivity of ESCC cells to cisplatin and suppressed NF-κB signaling activation and target gene expression.
- Blocking the NF-κB pathway abolished all observed effects of TAPI-1 on ESCC cells.
Conclusions:
- TAPI-1 impairs ESCC cell viability, migration, and invasion, and facilitates cisplatin-induced apoptosis through NF-κB signaling suppression.
- TAPI-1 demonstrates potential as an adjuvant therapeutic agent in combination with cisplatin for ESCC treatment.
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