title: Inhibition of livin expression suppresses cell proliferation and enhances chemosensitivity to cisplatin in human lung adenocarcinoma cells.
abstract: Livin is a novel member of the inhibitor of apoptosis protein family that has been reported to be overexpressed in various types of human malignancy. Although several studies have demonstrated that livin may be used as an effective target for tumor therapy, few studies have investigated its role in human lung adenocarcinoma. In the present study, two different methods were used in order to investigate the tumor‑suppressing effect of livin in human lung adenocarcinoma cells. Firstly, small interfering (si)RNA technology was used to down regulate livin expression; siRNA-mediated knockdown of livin was confirmed using reverse transcription quantitative polymerase chain reaction and western blot analysis, and cell proliferations was assessed using an MTT assay in vitro. Secondly, inhibition of livin expression was induced through the synergistic inhibitory effect between flavopiridol and tumor necrosis factor‑related apoptosis-inducing ligand (TRAIL). Experimental results revealed that, following transfection of the livin gene-silencing vector, the gene expression of livin was markedly decreased, SPC-A1 cell proliferation was significantly reduced and the therapeutic effect of the chemotherapy drug cisplatin was markedly improved. This growth inhibitory effect was also observed in the flavopiridol and TRAIL combination treatment group. In the flavopiridol and TRAIL combination treatment group, the protein expression of livin was significantly reduced and the survival rate of SPC‑A1 cells was significantly lower than the flavopiridol and TRAIL single operation group. In conclusion, the RNA silencing and the synergistic inhibitory effect between flavopiridol with TRAIL was able to effectively inhibit the expression of livin, significantly decrease SPC-A1 tumor cell proliferation and significantly enhance sensitivity to the chemotherapy drug cisplatin. These findings suggest that livin may be used as a novel target for tumor gene therapy.
authors.affiliation: Department of Medical Oncology, Yunnan Cancer Hospital, Kunming Medical University, Kunming, Yunnan 650118, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhuang
authors.affiliation: Department of Medical Oncology, Yunnan Cancer Hospital, Kunming Medical University, Kunming, Yunnan 650118, P.R. China.
authors.forename: Li-Da
authors.initials: LD
authors.lastname: Shen
authors.affiliation: Department of Medical Oncology, Yunnan Cancer Hospital, Kunming Medical University, Kunming, Yunnan 650118, P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Yunnan Cancer Hospital, Kunming Medical University, Kunming, Yunnan 650118, P.R. China.
authors.forename: Run-Xiang
authors.initials: RX
authors.lastname: Yang
authors.affiliation: Department of Medical Oncology, Yunnan Cancer Hospital, Kunming Medical University, Kunming, Yunnan 650118, P.R. China.
authors.forename: Qin-Yong
authors.initials: QY
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Yunnan Cancer Hospital, Kunming Medical University, Kunming, Yunnan 650118, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Yunnan Cancer Hospital, Kunming Medical University, Kunming, Yunnan 650118, P.R. China.
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Gao
authors.affiliation: Department of Medical Oncology, Yunnan Cancer Hospital, Kunming Medical University, Kunming, Yunnan 650118, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Dong
authors.affiliation: Department of Medical Oncology, Yunnan Cancer Hospital, Kunming Medical University, Kunming, Yunnan 650118, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Bi
authors.affiliation: Department of Medical Oncology, Yunnan Cancer Hospital, Kunming Medical University, Kunming, Yunnan 650118, P.R. China.
authors.forename: Jing-Nan
authors.initials: JN
authors.lastname: Tao
authors.affiliation: Department of Medical Oncology, Yunnan Cancer Hospital, Kunming Medical University, Kunming, Yunnan 650118, P.R. China.
authors.forename: Xiao-Nan
authors.initials: XN
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The First People's Hospital of Kunming, Yunnan 650011, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002945:Cisplatin / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C419866:BIRC7 protein, human; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D002945:Cisplatin