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29 April 2016 : Laboratory Research  

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

XinHai ZhuBE, Hao JiangABCDEFG, Jinhui LiCE, Ji XuCD, Zhenghua FeiCF

DOI: 10.12659/MSM.898558

Med Sci Monit 2016; 22:1435-1441

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

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750