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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

Saikosaponin-A Exhibits Antipancreatic Cancer Activity by Targeting the EGFR/PI3K/Akt Pathway

Author(s): Chengda Shi, Linglin Sun, Rong Fang, Shuying Zheng, Mingming Yu and Qiang Li*

Volume 24, Issue 4, 2023

Published on: 13 September, 2022

Page: [579 - 588] Pages: 10

DOI: 10.2174/1389201023666220610113514

Price: $65

Abstract

Background: A diagnosis of pancreatic cancer is pretty grim. Saikosaponin-A (SSA) is a Chinese herbal extract with anticancer activity. However, the therapeutic effect of SSA on pancreatic cancer remains elusive.

Aim: The study aims to evaluate the antitumor effects of SSA on pancreatic cancer cells in vitro and in vivo.

Methods: After treatment with SSA, cell viability was measured using the CCK-8 assay, DAPI staining was performed to analyze the effect on nuclear morphology, propidium iodide (PI) staining was used to detect the cell cycle, and Annexin V/PI double staining was conducted to analyze apoptosis. Then, the expression of apoptosis-related proteins and EGFR/PI3K/Akt pathway-related proteins was determined using western blotting. The binding of SSA to EGFR was analyzed by performing molecular docking. The mouse pancreatic cancer model was established by subcutaneously injecting pancreatic cancer cells, and after 30 days of SSA gavage, the tumor volume was calculated. Tumor tissue sections were subjected to Ki67 immunohistochemical staining and HE staining.

Results: SSA inhibited the proliferation of pancreatic cancer cells. As the concentration of SSA increased, the proportions of BxPC-3 and MIA PaCa-2 cells in the G0/G1 phase increased, the proportions of early and late apoptotic cells also increased, and the apoptosis rate gradually increased. Apoptosis inhibitor experiments indicated that SSA promoted the activation of caspase 3 to induce apoptosis in pancreatic cancer cells. In addition, SSA treatment significantly reduced the levels of phosphorylated EGFR, Akt, and PI3K in the two cell lines. Molecular docking results showed that SSA may have potential binding sites in EGFR. Results of the xenograft experiment confirmed the antitumor effects of SSA, as evidenced by the decreased tumor weight and downregulated expression of Ki67.

Conclusion: The results revealed that SSA exerted inhibitory effects on pancreatic cancer cells. These effects may be related to the inactivation of the EGFR/PI3K/Akt signalling pathway.

Keywords: Saikosaponin-A, pancreatic cancer, EGFR/PI3K/Akt pathway, cell cycle, apoptosis, identification.

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