Genetic transfer of PNAS-4 induces apoptosis and enhances sensitivity to gemcitabine in lung cancer.
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.
Hou
Shengyan
S
West China Hospital, Sichuan University, Chengdu, PR China.
Zhao
Zhiwei
Z
Yan
Fei
F
Chen
Xiancheng
X
Deng
Hongxin
H
Chen
Xiang
X
Wang
Yongsheng
Y
Wei
Yuquan
Y
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D019759:Carbon-Nitrogen Lyases; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D014183:Transplantation, Heterologous; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D051017:Apoptosis Regulatory Proteins; D003841:Deoxycytidine; D019759:Carbon-Nitrogen Lyases; C000604991:DESI2 protein, human; D000093542:Gemcitabine