Affiliation:
1. Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Shanghai Cancer Center, Shanghai,
China
2. Shanghai Key Laboratory of Radiation Oncology (20dz2261000), Shanghai Engineering Research Center of Proton and
Heavy Ion Radiation Therapy, Shanghai, China
3. Shanghai Engineering Research Center of Proton and
Heavy Ion Radiation Therapy, China
4. Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center,
Shanghai, China
Abstract
Background:
Salivary Adenoid Cystic Carcinoma (ACC) is characterized by a highly invasive and
slow-growing pattern, and its etiology remains unidentified. Triptonide (TN) has demonstrated efficacy as a
pharmacotherapeutic agent against ACC. Nonetheless, the specific targets and mechanism of molecular action
underlying the effectiveness of TN in treating ACC have not been elucidated.
Objectives:
By integrating network pharmacology within laboratory experiments, this research delves into the
prospective targets and molecular mechanisms associated with the application of TN in treating ACC.
Methods:
Initially, pertinent targets associated with TN against ACC were acquired from public databases.
Subsequently, a combination of network pharmacology and bioinformatics analysis was utilized to screen the
top 10 hub targets and key signal pathways of TN-treating ACC. Finally, in vitro experiments involving various
molecular assays were conducted to evaluate the biological phenotypes of cells following TN treatment,
encompassing assessments of apoptosis levels, plate migration, and other parameters, thereby validating pivotal
genes and pathways.
Results:
A total of 23 pertinent targets for TN in relation to ACC were identified, with the top 10 hub genes being
MAPK8, PTGS2, RELA, MAPK14, NR3C1, HDAC1, PPARG, NFKBIA, AR, and PGR. There was a significant
correlation between the TNF signaling pathway and the treatment of ACC with TN. In vitro experiments
demonstrated that TN treatment elevated RELA phosphorylation while concurrently reducing MAPK14
phosphorylation and inducing G2/M arrest. TN exhibited the ability to enhance the apoptosis rate through increased
caspase-3 activity, elevated levels of Reactive Oxygen Species (ROS), mitochondrial dysfunction, and
inhibition of cell migration.
Conclusion:
There is a potential therapeutic role for TN in the treatment of ACC through the activation of the
TNF signaling pathway. Among the identified candidates, MAPK8, HDAC1, PTGS2, RELA, NR3C1,
PPARG, NFKBIA, AR, and PGR emerge as the most pertinent therapeutic targets for TN in the context of
ACC treatment.
Publisher
Bentham Science Publishers Ltd.