title: siRNA suppression of hTERT using activatable cell-penetrating peptides in hepatoma cells.
abstract: Activatable cell-penetrating peptides (aCPPs) allow non-viral, low cytotoxic and selective delivery of compounds into target cells for cancer therapy. In tumour cells, up-regulation of human telomerase reverse transcriptase (hTERT) frequently occurs and is being considered as a target in cancer diagnosis and treatment. siRNA sequence that target hTERT mRNA can silence the gene and reduce hTERT protein expression to reduce cell proliferation and inhibit cell growth. In our study, we tested a matrix metalloproteinase-2 (MPP2) aCPP in delivering hTERT siRNA into hepatocellular carcinoma cells (SMMC-7721) to silence the hTERT gene. Cultured SMMC-7721 cells were transfected with a complex of aCPPs and hTERT-specific siRNA-encoding or control plasmids. Compared with cells treated with the complex of control plasmid-CPPs, cells treated with the hTERT-specific siRNA-encoding plasmid-CPP complex had a prolonged G1-phase, but a shorter G2/S-phase, indicating a G1-arrest. Treatment with the hTERT-specific siRNA resulted in a significant decrease (by 26%; P<0.05) in hTERT mRNA levels. The aCPPs tested in this study provides a non-viral delivery of siRNA into cancer cells to silence target genes in cancer therapy.
authors: *Department of Hepatic Surgery, the Third Affiliated hospital, Sun Yat-san University, Guangzhou 510630, China.
authors: Hua
authors: H
authors: Li
authors: *Department of Hepatic Surgery, the Third Affiliated hospital, Sun Yat-san University, Guangzhou 510630, China.
authors: Jiwen
authors: J
authors: He
authors: *Department of Hepatic Surgery, the Third Affiliated hospital, Sun Yat-san University, Guangzhou 510630, China.
authors: Huimin
authors: H
authors: Yi
authors: †Department of General Surgery, Guangdong No. 2 Provincial People's Hospital, Guangzhou 510317, China.
authors: Guoan
authors: G
authors: Xiang
authors: †Department of General Surgery, Guangdong No. 2 Provincial People's Hospital, Guangzhou 510317, China.
authors: Kaiyun
authors: K
authors: Chen
authors: *Department of Hepatic Surgery, the Third Affiliated hospital, Sun Yat-san University, Guangzhou 510630, China.
authors: Binsheng
authors: B
authors: Fu
authors: *Department of Hepatic Surgery, the Third Affiliated hospital, Sun Yat-san University, Guangzhou 510630, China.
authors: Yang
authors: Y
authors: Yang
authors: *Department of Hepatic Surgery, the Third Affiliated hospital, Sun Yat-san University, Guangzhou 510630, China.
authors: Guihua
authors: G
authors: Chen
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D034741:RNA, Small Interfering / Q000737:chemistry / Q000494:pharmacology*; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection
chemical_list: D057846:Cell-Penetrating Peptides; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C509186:TERT protein, human; D019098:Telomerase; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2