title: Anticancer Effects of Paris Saponins by Apoptosis and PI3K/AKT Pathway in Gefitinib-Resistant Non-Small Cell Lung Cancer.
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.
authors.affiliation: Department of Thoracic Surgery, Zhejiang Hospital, Hangzhou, Zhejiang, China (mainland).
authors.forename: XinHai
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Oncology, Zhejiang Hospital, Hangzhou, Zhejiang, China (mainland).
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Chinese Medicine and Rehabilitation, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China (mainland).
authors.forename: Jinhui
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Surgery, Huashan Luxeme Medical Cosmetology Hospital, Hangzhou, Zhejiang, China (mainland).
authors.forename: Ji
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Oncology, The First Clinical Medical Institute, Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland).
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Fei
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D000077156:Gefitinib; D006801:Humans; D020128:Inhibitory Concentration 50; D019668:Liliaceae / Q000737:chemistry*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011799:Quinazolines / Q000494:pharmacology*; D012503:Saponins / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D012503:Saponins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000077156:Gefitinib