title: Cationic liposome-mediated nitric oxide synthase gene therapy enhances             the antitumor effects of cisplatin in lung cancer.
abstract: Cisplatin is one of the most effective antitumor drugs for non-small cell             lung carcinoma (NSCLC) patients. However, its efficacy has encountered a plateau             due to its side effects and drug resistance. Inducible nitric oxide (NO) synthase             (iNOS) gene therapy has been reported to have antitumor effects in several types             of cancers and enhances sensitivity to cisplatin, but the effects of iNOS gene             therapy alone or its combination with cisplatin in lung cancer remain unclear.             In the current study, we evaluated the effects of cationic liposome (LP)-mediated             iNOS gene transfection on enhancing low-dose cisplatin-mediated antitumor effects             in the A549 human lung adenocarcinoma cell line in vitro. Furthermore, we examined             whether iNOS gene therapy enhances the antitumor effects of low-dose cisplatin             in two A549 human lung cancer cell xenograft mouse models. The results revealed             that iNOS gene therapy may significantly enhance low-dose cisplatin-mediated inhibition             of cell proliferation, invasion, migration and promotion of cell apoptosis in             A549 cells. Intratumoral administration of the LP-pVAX-iNOS complex significantly             enhanced low-dose cisplatin-mediated suppression of subcutaneous tumor growth.             Moreover, intravenous injection of the LP-pVAX-iNOS complex greatly enhanced low-dose             cisplatin-mediated inhibition of experimental lung metastasis and prolonged the             life span of mice without significant organ-related toxicity in a nude mouse model             of lung metastasis compared to the cisplatin alone-treated group. Furthermore,             iNOS gene-mediated enhancement of cisplatin-mediated antitumor effects in lung             cancer may be related to the attenuation of p-mTOR, MMP2 and the activation of             p-p53. Thus, the combination treatment with iNOS gene therapy and cisplatin may             be a novel and effective therapeutic strategy for lung cancer.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Sujuan
authors.initials: S
authors.lastname: Ye
authors.forename: Weihan
authors.initials: W
authors.lastname: Yang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Wenjing
authors.initials: W
authors.lastname: Ou
authors.forename: Qingping
authors.initials: Q
authors.lastname: Ma
authors.forename: Chuanjiang
authors.initials: C
authors.lastname: Yu
authors.forename: Jiang
authors.initials: J
authors.lastname: Ren
authors.forename: Guoxing
authors.initials: G
authors.lastname: Zhong
authors.forename: Huashan
authors.initials: H
authors.lastname: Shi
authors.forename: Zhu
authors.initials: Z
authors.lastname: Yuan
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Su
authors.forename: Wen
authors.initials: W
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D008081:Liposomes / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D016159:Tumor Suppressor Protein p53; D052247:Nitric Oxide Synthase Type II; D058570:TOR Serine-Threonine Kinases; D020778:Matrix Metalloproteinase 2; D002945:Cisplatin