title: Enhanced gemcitabine-mediated cell killing of human lung adenocarcinoma by vector-based RNA interference against PLK1.
abstract: Specific PLK1 silencing may be an effective gene therapy modality of treating PLK1-overexpressed cancers. In this study, we first explored the anticancer efficacy of three different short hairpin-expressing plasmids targeting PLK1 in animal model, and then determined the combination therapy effect of gemcitabine with PLK1-shRNA as an adjuvant. Transfection of the PLK1-shRNAs to A549 lung cancer cells induced significant PLK1 depletion, growth inhibition and apoptosis. In vivo administration of PLK1-shRNA constructs to tumor-bearing mice resulted in xenograft regression. Moreover, the combination of PLK1-shRNA plus low-dose gemcitabine (GEM) produced an additive antitumor activity on the lung tumors owing to an inhibition of cancer cell survival and augmented apoptosis. These results indicated a feasible bio-chemotherapeutic strategy for cancer.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Centre, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Zhao
authors.forename: Chun-Lai
authors.initials: CL
authors.lastname: Nie
authors.forename: Shu-Fang
authors.initials: SF
authors.lastname: Liang
authors.forename: Zhu
authors.initials: Z
authors.lastname: Yuan
authors.forename: Hong-Xin
authors.initials: HX
authors.lastname: Deng
authors.forename: Yu-Quan
authors.initials: YQ
authors.lastname: Wei
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007150:Immunohistochemistry; D008081:Liposomes; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D010957:Plasmids; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine; D000097869:Polo-Like Kinase 1
chemical_list: D000964:Antimetabolites, Antineoplastic; D018797:Cell Cycle Proteins; D003841:Deoxycytidine; D008081:Liposomes; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000093542:Gemcitabine; D000097869:Polo-Like Kinase 1