title: Knockdown of ribosomal protein L39 by RNA interference inhibits the growth of human pancreatic cancer cells in vitro and in vivo.
abstract: Pancreatic cancer remains a major unsolved health problem lacking a potent therapeutic option. Our previous studies showed that the ribosomal protein L39 (RPL39) gene was up-regulated after long-term silencing of oncogenic KRAS in pancreatic cancer PANC-1 cells, which indicated that RPL39 may be important for pancreatic cancer development and survival. In the current study, small interfering RNA (siRNA) targeting of the RPL39 gene was performed to determine the effects of the RPL39 gene on growth of pancreatic cancer PANC-1 and BxPC-3 cells in vitro and in vivo. Results from in vitro experiments showed that knockdown of RPL39 expression with RPL39-siRNA suppressed cell proliferation and specifically enhanced cell apoptosis significantly in both PANC-1 and BxPC-3 cells. The increase of caspase-8 activities and the loss of mitochondrial membrane potential after RPL39 silencing indicated that the RPL39 gene may be involved in caspase-8-related mitochondrial apoptosis. Further, treatment with the RPL39-siRNA inhibited the growth of a human pancreatic cancer xenograft in BALB/c nude mice, accompanied by a decreased expression of RPL39. In the xenograft tumors with injection of RPL39-siRNA, the expressions of Ki-67 and CD31 were significantly down-regulated, and apoptosis was markedly induced. Our findings suggested that siRNA against the RPL39 gene may be of value for gene therapy of pancreatic cancer.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of China; Engineering Research Center for Cell Engineering and Therapeutic Antibody, SJTU, Shanghai, People's Republic of China.
authors.forename: Chaodong
authors.initials: C
authors.lastname: Li
authors.forename: Daijie
authors.initials: D
authors.lastname: Chen
authors.forename: Minyu
authors.initials: M
authors.lastname: Luo
authors.forename: Mei
authors.initials: M
authors.lastname: Ge
authors.forename: Jianwei
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; D012269:Ribosomal Proteins; C040223:ribosomal protein L39
keywords: Cell growth; Pancreatic cancer; RNA interference; RPL39; Tumor xenograft