2. Academic Validation
  3. The potential effect and mechanism of Saikosaponin A against gastric cancer

The potential effect and mechanism of Saikosaponin A against gastric cancer

  • BMC Complement Med Ther. 2023 Aug 22;23(1):295. doi: 10.1186/s12906-023-04108-3.
Chao Wang 1,  Ruijuan Zhang 2,  Xu Chen 2,  Mengyun Yuan 2,  Jian Wu 3,  Qingmin Sun 3,  Chunrun Miao 4,  Yali Jing 5 6
Affiliations

Affiliations

  • 1 China Pharmaceutical University, Nanjing Drum Tower Hospital, Nanjing, 210008, Jiangsu Province, China.
  • 2 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China.
  • 3 Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, Jiangsu, China.
  • 4 Department of Gastroenterology, Dongtai Hospital of Traditional Chinese Medicine, Dongtai, 224299, Jiangsu, China. [email protected].
  • 5 China Pharmaceutical University, Nanjing Drum Tower Hospital, Nanjing, 210008, Jiangsu Province, China. [email protected].
  • 6 Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu, China. [email protected].
PMID: 37608281 DOI: 10.1186/s12906-023-04108-3
Abstract

Background: Saikosaponin A (SSA) shows a series of pharmacological activities, such as anti-inflammatory, antioxidant and antitumor. However, there is a lack of comprehensive research or sufficient evidence regarding the efficacy of SSA in treating gastric Cancer (GC), and the specific mechanisms by which it inhibits GC growth and progression are still not fully understood.

Methods: MTT and clonogenic assays were employed to detect the effect of SSA on the proliferation of GC cells. Bioinformatics predicted the SSA targets in the treatment of GC. The core genes and the underlying mechanism of SSA in anti-GC were obtained by analyzing the intersecting targets; molecular docking and Western blot were used to check the reliability of core genes. Flow cytometry was used to analyze Apoptosis and cell cycle in GC cells treated with varying concentrations of SSA. Western blot was employed to detect the expression levels of related proteins.

Results: SSA significantly blocked GC cells in the S phase of the cell cycle and induced Apoptosis to suppress the proliferation of GC cells. Network pharmacology revealed that the underlying mechanisms through which SSA acts against GC involve the modulation of several signaling pathways, including the PI3K-Akt, MAPK, Ras, and T-cell signaling pathways. Molecular docking showed pivotal target genes with a high affinity to SSA, including STAT3, MYC, TNF, STAT5B, Caspase-3 and Src. Furthermore, western blot results revealed that SSA significantly increased the protein levels of Bax and Cleaved Caspase-3, whereas decreased the expression levels of p-JAK, p-STAT3, MYC, Bcl-2, p-PI3K, p-AKT and p-mTOR, confirming that the reliability of hub targets and SSA could promote GC cell Apoptosis by suppressing PI3K/Akt/mTOR pathway.

Conclusions: The results suggest that SSA has the ability to trigger Apoptosis in GC cells by blocking the PI3K/Akt/mTOR pathway. These findings highlight the potential of SSA as a promising natural therapeutic agent for the treatment of GC.

Keywords

Apoptosis; Gastric cancer; Network pharmacology; Saikosaponin A.

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