International journal of molecular medicine, 2013-01, Vol.31 (1), p.33-42
2013
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- Autor(en) / Beteiligte
- Titel
- Cationic liposome-mediated nitric oxide synthase gene therapy enhances the antitumor effects of cisplatin in lung cancer
- Ist Teil von
- International journal of molecular medicine, 2013-01, Vol.31 (1), p.33-42
- Ort / Verlag
- Greece: D.A. Spandidos
- Erscheinungsjahr
- 2013
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1107-3756eISSN: 1791-244XDOI: 10.3892/ijmm.2012.1171Titel-ID: cdi_proquest_journals_1932350301
- Format
- –
- Schlagworte
- A549, Animals, Antineoplastic Agents - pharmacology, Antineoplastic Combined Chemotherapy Protocols - pharmacology, Apoptosis, Apoptosis - drug effects, Cancer therapies, Carcinoma, Non-Small-Cell Lung - drug therapy, cationic liposomes, Cell cycle, Cell growth, Cell Line, Tumor, Cell Proliferation - drug effects, cisplatin, Cisplatin - pharmacology, combination treatment, Cytokines, Deoxyribonucleic acid, DNA, Dose-Response Relationship, Drug, Drug dosages, Drug Synergism, Female, Gene expression, Gene therapy, Genetic Therapy, Humans, iNOS, Kinases, Laboratory animals, Liposomes - pharmacology, Lung cancer, Matrix Metalloproteinase 2 - genetics, Matrix Metalloproteinase 2 - metabolism, Metastasis, Mice, Mice, Inbred BALB C, Mice, Nude, Nitric oxide, Nitric Oxide Synthase Type II - genetics, Nitric Oxide Synthase Type II - metabolism, Ovarian cancer, Plasmids, Prostate, Protein expression, Proteins, Rodents, Studies, Thyroid cancer, TOR Serine-Threonine Kinases - genetics, TOR Serine-Threonine Kinases - metabolism, Tumor Suppressor Protein p53 - genetics, Tumor Suppressor Protein p53 - metabolism, Tumors, Xenograft Model Antitumor Assays - methods