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Med Sci Monit. 2016 Apr 29;22:1435-41.

Anticancer Effects of Paris Saponins by Apoptosis and PI3K/AKT Pathway in Gefitinib-Resistant Non-Small Cell Lung Cancer.

Author information

1
Department of Thoracic Surgery, Zhejiang Hospital, Hangzhou, Zhejiang, China (mainland).
2
Department of Oncology, Zhejiang Hospital, Hangzhou, Zhejiang, China (mainland).
3
Department of Chinese Medicine and Rehabilitation, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China (mainland).
4
Department of Surgery, Huashan Luxeme Medical Cosmetology Hospital, Hangzhou, Zhejiang, China (mainland).
5
Department of Oncology, The First Clinical Medical Institute, Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland).

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.

PMID:
27125283
PMCID:
PMC4917328
[Indexed for MEDLINE]
Free PMC Article

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