Saikosaponin D overcomes gemcitabine resistance in pancreatic cancer via AKT/mTOR pathway inhibition and synergistic induction of apoptosis and autophagy
Year: 2025
Type: article
Abstract: root, exhibits anti‑inflammatory and antitumor properties; however, to the best of our knowledge, its role in pancreatic cancer and GEM sensitization remains unclear. The present study investigated the effects of SSD on the proliferation, apoptosis and autophagy of pancreatic cancer cells, and evaluated whether SSD can overcome GEM resistance to enhance its antitumor effects. Using MIA PaCa‑2 and AsPC‑1 cells, the sensitivity to SSD and GEM was assessed using Cell Counting Kit‑8 assays, H&E staining and colony formation assays. Optimal sub‑lethal concentrations of GEM (0.25 µmol/l), SSD (4 µmol/l) and their combination (0.25 µmol/l GEM + 4 µmol/l SSD) were identified. Apoptosis was evaluated through Hoechst 33258 staining and TUNEL assays, while autophagy was measured using the monodasylcadaverine method. Western blotting and immunocytochemical staining were used to analyze the expression levels of proteins related to apoptosis, AKT/mTOR signaling and autophagy. The results demonstrated that the SSD + GEM combination significantly inhibited pancreatic cancer cell proliferation in both MIA PaCa‑2 and AsPC‑1 cell lines, with proliferation being suppressed by nearly half. Similarly, the combination treatment induced apoptosis and enhanced autophagosome formation, suggesting potential synergistic effects when compared with GEM monotherapy. In conclusion, SSD synergistically enhanced the antitumor effects of GEM by inhibiting pancreatic cancer cell proliferation, and inducing apoptosis and autophagy. SSD may overcome GEM resistance by sensitizing cells through AKT/mTOR pathway inhibition.
Source: Oncology Reports
DOI: 10.3892/or.2025.9033
Authors: Rui Zheng, Yusi Liu, Sen Zhou, Guimei Liu, Xiaobin Liu, Yiyuan Yang, Yufu Zhang
Institutions: Yan'an University, Yanan University Affiliated Hospital
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4417076218
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