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Genetic transfer of PNAS‐4 induces apoptosis and enhances sensitivity to gemcitabine in lung cancer
Author(s) -
Hou Shengyan,
Zhao Zhiwei,
Yan Fei,
Chen Xiancheng,
Deng Hongxin,
Chen Xiang,
Wang Yongsheng,
Wei Yuquan
Publication year - 2009
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1016/j.cellbi.2008.11.014
Subject(s) - gemcitabine , apoptosis , in vivo , lung cancer , cancer research , mtt assay , cytotoxicity , pharmacology , cancer cell , chemistry , in vitro , cancer , medicine , biology , oncology , biochemistry , microbiology and biotechnology
PNAS‐4 has been demonstrated to induce apoptosis in U2OS cells. To evaluate its feasibility as a new strategy for cancer therapy, we analyzed its anti‐tumor effect with or without gemcitabine in A549 lung cancer cells. MTT assay, Hoechst 33258 staining and flow cytometric analysis were used to determine the cytotoxicity of PNAS‐4 alone or plus gemcitabine. The anti‐tumor efficacy was further investigated in vivo with nude mice. PNAS‐4 plasmid/liposome complexes were injected by tail vein every 4 days. Gemcitabine was given ip on a weekly schedule for 4 weeks. PNAS‐4 alone and plus gemcitabine induced apoptosis in A549 cells in vitro. The xenograft lung cancer treated with PNAS‐4 retarded growth compared with the empty vector. The combination of PNAS‐4 with gemcitabine induced anti‐tumor activity accompanied by an increase in apoptotic cells compared with PNAS‐4 or gemcitabine alone. No other obvious toxicity was found. PNAS‐4 therefore suppresses tumor growth in vivo and enhances sensitivity to gemcitabine. This suggests that the PNAS‐4 gene could be a potential candidate for lung cancer therapy alone or in combination with gemcitabine.