title: Paris Saponins enhance radiosensitivity in a gefitinib-resistant lung adenocarcinoma cell line by inducing apoptosis and G2/M cell cycle phase arrest.
abstract: Acquired resistance to epidermal growth factor inhibitors has been reported to be associated with cross‑resistance to radiation. Paris Saponins (PSs) exert a wide range of pharmacological activities, including cell apoptosis induction, multidrug resistance inhibition, angiogenesis inhibition and tumor cell migration by modulating various signaling pathways. The present study aimed to investigate the radiosensitization effects of PSII, PSVI and PSVII in a gefitinib‑resistant PC‑9‑ZD lung adenocarcinoma cell line, and the possible mechanism underlying their function. A clonogenic assay was performed to determine the effects of PS radiosensitization on the PC‑9‑ZD cell line. The cell cycle was analyzed by flow cytometry, and cell apoptosis was analyzed with Annexin V/propidium iodide and Hoechst staining. Protein expression levels were detected by western blotting. The results of the present study revealed a significant increase in PC‑9‑ZD cell line radiosensitivity following treatment with PSs. PSs induced G2/M cell cycle phase arrest and apoptosis of the irradiated PC‑9‑ZD cells. Notably, the expression levels of B cell lymphoma 2 (Bcl‑2) were downregulated, and those of caspase‑3, Bcl‑2‑associated X protein (Bax) and p21/Waf1/Cip1 were upregulated following treatment with PSs. The present results demonstrated that PSs induced radiosensitivity in gefitinib‑resistant cells by inducing G2/M phase arrest and by enhancing the apoptotic response via the modulation of caspase‑3, Bax, Bcl‑2 and p21/Waf1/Cip1 expression.
authors: Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 310002, P.R. China.
authors: Peng-Jun
authors: PJ
authors: Zhao
authors: Department of Gastroenterology, 117 Hospital of People's Liberation Army, Hangzhou, Zhejiang 310013, P.R. China.
authors: Shui-Chuan
authors: SC
authors: Song
authors: Department of Gastroenterology, 117 Hospital of People's Liberation Army, Hangzhou, Zhejiang 310013, P.R. China.
authors: Lei-Wen
authors: LW
authors: Du
authors: Department of Oncology, Anji People's Hospital, Anji, Zhejiang 313399, P.R. China.
authors: Guo-Hua
authors: GH
authors: Zhou
authors: Department of Oncology, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310006, P.R. China.
authors: Sheng-Lin
authors: SL
authors: Ma
authors: Department of Chinese Medicine and Rehabilitation, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China.
authors: Jin-Hui
authors: JH
authors: Li
authors: Department of Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.
authors: Jian-Guo
authors: JG
authors: Feng
authors: Department of Thoracic Surgery, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China.
authors: Xin-Hai
authors: XH
authors: Zhu
authors: Department of Oncology, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China.
authors: Hao
authors: H
authors: Jiang
mesh_terms: D000230:Adenocarcinoma / Q000532:radiotherapy; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000532:radiotherapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D011836:Radiation Tolerance / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012503:Saponins / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; C000595707:BCL2 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C000596536:Paris saponin VII; D019253:Proto-Oncogene Proteins c-bcl-2; D011799:Quinazolines; D011838:Radiation-Sensitizing Agents; D012503:Saponins; D051028:bcl-2-Associated X Protein; C067584:formosanin C; C505407:CASP3 protein, human; D053148:Caspase 3; D004144:Diosgenin; D000077156:Gefitinib