title: [Small interfering RNA targeting STAT3 enhances antitumor activity of doxorubicin].
abstract: This study is to investigate the effect of small interfering RNA targeting STAT3 (STAT3-siRNA) enhancing antitumor activity of doxorubicin. RT-PCR and Western blotting were used to test the expression of STAT3 mRNA and protein in the HepG2, HeLa and K562/DOX cells and the effect of STAT3-siRNA on the expression of STAT3 mRNA and protein. MTT and Trypan blue assay were performed to determine the inhibitory effect of STAT3-siRNA on HepG2, HeLa and K562/DOX cells and the effect of STAT3-siRNA enhancing antitumor activity of doxorubicin. The effects of STAT3-siRNA on intracellular accumulation of doxorubicin and cell apoptosis were performed by Arrary Scan V(TI)HCS600 High-Contents. The results showed that STAT3 gene, STAT3 and pSTAT3 protein were highly expressed in HepG2, HeLa and K562/DOX cells and STAT3-siRNA decreased the expression of STAT3 mRNA and protein. STAT3-siRNA inhibited the growth of HepG2, HeLa and K562/DOX cells. STAT3-siRNA in combination with doxorubicin decreased by 3.13, 5.22 and 1.74 fold of IC50 of HepG2, HeLa and K562/DOX cells compared with doxorubicin only. Intracellular accumulation of doxorubicin increased by 16.8%, 12.87% and 25.67% respectively in HepG2, HeLa and K562/DOX cells in the presence of STAT3-siRNA. An enhancement of doxorubicin-induced cell apoptosis was observed in HepG2, HeLa and K562/DOX cells treated with STAT3-siRNA. The results suggested that STAT3-siRNA could enhance the antitumor activity of doxorubicin on HepG2, HeLa and K562/DOX cells.
authors.affiliation: Institute of Chinese Materia Medica, College of Pharmacy, Henan University, Kaifeng 475004, China. wtx1975@126.com
authors.forename: Tian-Xiao
authors.initials: TX
authors.lastname: Wang
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Wang
authors.forename: Zhong-Qing
authors.initials: ZQ
authors.lastname: Zhang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology*; D004357:Drug Synergism; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D020014:K562 Cells; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D000903:Antibiotics, Antineoplastic; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D004317:Doxorubicin