Abstract
BACKGROUND: Paris saponins have been studied for their anticancer effects in various cancer types, but the mechanisms underlying the cytotoxic effects, especially in EGFR-TKI-resistant cells, are still unclear. We explored the potential mechanism of the antitumor effects of PSI, II, VI, VII in EGFR-TKI-resistant cells and attempted to develop PSI, II, VI, VII as a systemic treatment strategy for EGFR-TKI-resistant lung cancer.
MATERIAL AND METHODS: Growth inhibition was detected by MTT assay. The apoptosis assay was detected using annexin-V/PI and Hoechst staining. The level of PI3K, pAKT, Bax, Bcl-2, caspase-3, and caspase-9 protein expression were detected using Western blot analysis.
RESULTS: The results revealed that PSI, II, VI, VII inhibited the proliferation of PC-9-ZD cells. Furthermore, PSI, II, VI, VII induced significant cell apoptosis. The levels of PI3K, pAKT, Bcl-2 protein decreased, while the Bax, caspase-3, and caspase-9 protein was increased by PSI, II, PSVI, PSVII treatment and resulted in increased sensitivity to gefitinib in PC-9-ZD cells.
CONCLUSIONS: The underlying mechanism of Paris saponins may be related to targeting the PI3K/AKT pathways to cause apoptosis. Our results suggest a therapeutic potential of Paris saponins in clinical settings for gefitinib-resistant NSCLC.
Keywords: Antineoplastic Agents – therapeutic use, Carcinoma, Non-Small-Cell Lung – pathology, Cell Proliferation – drug effects, Drug Resistance, Neoplasm – drug effects, Inhibitory Concentration 50, Liliaceae – chemistry, Lung Neoplasms – pathology, Phosphatidylinositol 3-Kinases – metabolism, Proto-Oncogene Proteins c-akt – metabolism, Quinazolines – pharmacology, Saponins – therapeutic use, Signal Transduction – drug effects
