Effect of Paris saponin I on radiosensitivity in a gefitinib‑resistant lung adenocarcinoma cell line

Jiang,Hao; Zhao,Pengjun; Feng,Jianguo; Su,Dan; Ma,Shenglin

doi:10.3892/ol.2014.2020

Effect of Paris saponin I on radiosensitivity in a gefitinib‑resistant lung adenocarcinoma cell line

Authors:
- Hao Jiang
- Pengjun Zhao
- Jianguo Feng
- Dan Su
- Shenglin Ma
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Affiliations: Department of Oncology, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China, Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 310002, P.R. China, Department of Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China, Department of Oncology, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310006, P.R. China
Published online on: April 1, 2014 https://doi.org/10.3892/ol.2014.2020
Pages: 2059-2064

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Abstract

Previous studies have observed that Paris saponin I (PSI) exerts a wide range of pharmacological activities, including cytotoxic activity against a number of malignancies, such as non‑small cell lung cancers. The present study aimed to investigate the radiosensitization of PSI treatment on a gefitinib‑resistant lung adenocarcinoma cell line, PC‑9‑ZD, and its possible mechanism. A 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyl‑tetrazolium bromide assay was used to determine the growth inhibition effect of PSI. A clonogenic assay was performed to determine the radiosensitizing effect of PSI treatment on the PC‑9‑ZD cell line. A single‑hit multi‑target model was used to plot survival curves and calculate sensitizing enhancement ratios. The cell cycle was analyzed by flow cytometry and cell apoptosis was analyzed with fluorescein‑isothiocyanate‑Annexin V/propidium iodide and Hoechst staining. The expression levels of the proteins were detected by western blotting. There was a significant reduction observed in the proliferation of the PC‑9‑ZD cell lines that were treated with PSI. PSI enhanced the radiosensitivity of the PC‑9‑ZD cells with a sensitization enhancement ratio of 1.77. Furthermore, PSI induced G2/M arrest and apoptosis of the irradiated PC‑9‑ZD cells. Notably, B‑cell lymphoma 2 (Bcl‑2) was downregulated, and caspase‑3, Bcl‑2‑like protein 4 (Bax) and cyclin‑dependent kinase inhibitor 1 (P21waf1/cip1) were upregulated by the PSI treatment. The present study showed that PSI treatment exhibited potent radiosensitivity against gefitinib‑resistant PC‑9‑ZD cells in vitro. This radiosensitivity was associated with cell cycle arrest at the G2/M phase, and apoptosis via an increase in caspase‑3, Bax and P21waf1/cip1 as well as a decrease in Bcl‑2 production.

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