RRC ID 1972
著者 Yonesaka K, Tamura K, Kurata T, Satoh T, Ikeda M, Fukuoka M, Nakagawa K.
タイトル Small interfering RNA targeting survivin sensitizes lung cancer cell with mutant p53 to adriamycin.
ジャーナル Int J Cancer
Abstract Survivin is a member of the inhibitor of apoptosis protein (IAP) family that is specifically overexpressed in cancer tissues. p53 is one of the tumor suppressor genes; its induction in response to DNA damage causes apoptosis and correlates with drug sensitivity. To investigate the possible regulation of survivin by p53, we examined the level of survivin expression in lung cancer cell lines in response to adriamycin. Levels of survivin mRNA and protein in cell lines with wild-type p53 decreased dramatically after p53 induction, but no such reduction of survivin was observed in cell lines with mutated or null p53. Inhibition of wild-type p53 in A549 cells by small interfering (si) RNA significantly upregulated the expression of survivin. Survivin inhibition by siRNA in PC9 cells with mutated p53 significantly depressed cell proliferation. To investigate the sensitivity of cancer cells to adriamycin after inhibition of survivin, we depressed survivin expression using siRNA, and then added adriamycin at an IC50 dose. After a further 48 hr incubation with adriamycin, proliferation was significantly depressed in the cells treated with siRNA targeting survivin, in comparison with siRNA targeting scramble. Furthermore, both TUNEL and pro-caspase3 expression assay showed a significant increase in apoptosis after combined treatment with adriamycin and siRNA targeting survivin. Our results demonstrate that survivin is downregulated by p53, and that siRNA targeting of survivin increases cell sensitivity to adriamycin and promotes apoptosis. siRNA targeting of survivin could be potentially useful for increasing sensitivity to anticancer drugs, especially in drug-resistant cells with mutated p53.
巻・号 118(4)
ページ 812-20
公開日 2006-2-15
DOI 10.1002/ijc.21350
PMID 16108013
MeSH Antibiotics, Antineoplastic / pharmacology* Apoptosis / drug effects Apoptosis / genetics Doxorubicin / pharmacology* Gene Expression Regulation, Neoplastic Genes, p53 Humans In Situ Nick-End Labeling Inhibitor of Apoptosis Proteins Lung Neoplasms / genetics* Lung Neoplasms / pathology Microtubule-Associated Proteins / biosynthesis* Mutation Neoplasm Proteins / biosynthesis* RNA, Small Interfering Reverse Transcriptase Polymerase Chain Reaction Survivin Tumor Cells, Cultured Up-Regulation
IF 5.145
引用数 72
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 Lu-135(RCB0468)