Paris saponin I induces apoptosis via increasing the Bax/Bcl‑2 ratio and caspase‑3 expression in gefitinib‑resistant non‑small cell lung cancer in vitro and in vivo

Jiang,Hao; Zhao,Peng‑Jun; Su,Dan; Feng,Jianguo; Ma,Sheng‑Lin

doi:10.3892/mmr.2014.2108

Paris saponin I induces apoptosis via increasing the Bax/Bcl‑2 ratio and caspase‑3 expression in gefitinib‑resistant non‑small cell lung cancer in vitro and in vivo

Authors:
- Hao Jiang
- Peng‑Jun Zhao
- Dan Su
- Jianguo Feng
- Sheng‑Lin 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, Cancer Institute, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China, Department of Oncology, Cancer Institute, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China, Department of Oncology, Cancer Institute, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310006, P.R. China
Published online on: April 2, 2014 https://doi.org/10.3892/mmr.2014.2108
Pages: 2265-2272

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Abstract

Polyphyllins, a major component of Rhizoma paridis, have been extensively used in non‑small cell lung cancer (NSCLC). The aim of the present study was to evaluate the effects of Paris saponin I (PSI) on a panel of gefitinib‑resistant NSCLC cell lines and its inhibition of tumor growth in a nude mouse model. The MTT assay was used to assess growth inhibition. The cell cycle was analyzed using flow cytometry and apoptosis was assessed using Annexin V/propidium iodide staining. The morphology of the apoptotic cells was determined by transmission electron microscopy. The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax) and caspase‑3 were detected using western blot analysis. In addition, the glucose metabolism in tumor‑bearing mice was evaluated using 18F‑fludeoxyglucose (FDG) micro‑positron emission tomography imaging. The PSI‑induced growth inhibition rate was observed to significantly increase in a time‑ and dose‑dependent manner. Furthermore, PSI induced significant G2/M‑phase arrest and apoptosis. The expression levels of Bcl‑2 decreased, while those of Bax and caspase‑3 increased following PSI treatment. 18F‑FDG‑uptake in the PSI treatment groups was significantly decreased compared with that in the control group in vivo. In conclusion, PSI is a potent antitumor agent that acts by inhibiting the proliferation of gefitinib‑resistant cells, and has potential as a candidate for a natural drug for gefitinib‑resistant therapy. PSI‑induced apoptosis, which occurred via multiple pathways, including G2/M‑phase arrest and upregulation of the Bax/Bcl‑2 ratio and caspase‑3 expression, ultimately led to cell death and tumor inhibition.

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