Enhancement of cisplatin sensitivity in lewis lung carcinoma by liposome-mediated delivery of a survivin mutant
| Autor: | Yuan Wen, Li Pan, Huashan Shi, Xiang Chen, Zhi-Yong Li, Qing-Zhong Yuan, Chun-Ting Wang, Dan-Dan Yu, Fei Leng, Yuquan Wei |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
inorganic chemicals
Cancer Research Angiogenesis Survivin medicine.medical_treatment Antineoplastic Agents Apoptosis Biology lcsh:RC254-282 Inhibitor of Apoptosis Proteins Carcinoma Lewis Lung Mice Immune system medicine Animals neoplasms Sensitization Cisplatin Chemotherapy Neovascularization Pathologic Research Lewis lung carcinoma Drug Synergism Genetic Therapy lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Combined Modality Therapy Mice Inbred C57BL medicine.anatomical_structure Oncology Liposomes Mutation Cancer research Female Microtubule-Associated Proteins medicine.drug |
| Zdroj: | Journal of Experimental & Clinical Cancer Research, Vol 29, Iss 1, p 46 (2010) Journal of Experimental & Clinical Cancer Research : CR |
| ISSN: | 1756-9966 |
| DOI: | 10.1186/1756-9966-29-46 |
| Popis: | Background A high concentration of cisplatin (CDDP) induces apoptosis in many tumor cell lines. CDDP has been administered by infusion to avoid severe toxicity. Recently, it has been reported that changes in survivin expression or function may lead to tumor sensitization to chemical and physical agents. The aim of this study was to determine whether a dominant-negative mouse survivin mutant could enhance the anti-tumor activity of CDDP. Methods A plasmid encoding the phosphorylation-defective dominant-negative mouse survivin threonine 34→alanine mutant (survivin T34A) complexed to a DOTAP-chol liposome (Lip-mS) was administered with or without CDDP in Lewis Lung Carcinoma (LLC) cells and in mice bearing LLC tumors, and the effects on apoptosis, tumor growth and angiogenesis were assessed. Data were analyzed using one-way analysis of variance(ANOVA), and a value of P < 0.05 was considered to be statistically significant. Results LLC cells treated with a combination of Lip-mS and CDDP displayed increased apoptosis compared with those treated with Lip-mS or CDDP alone. In mice bearing LLC tumors and treated with intravenous injections of Lip-mS and/or CDDP, combination treatment significantly reduced the mean tumor volume compared with either treatment alone. Moreover, the antitumor effect of Lip-mS combined with CDDP was greater than their anticipated additive effects. Conclusion These data suggest that the dominant-negative survivin mutant, survivin T34A, sensitized LLC cells to chemotherapy of CDDP. The synergistic antitumor activity of the combination treatment may in part result from an increase in the apoptosis of tumor cells, inhibition of tumor angiogenesis and induction of a tumor-protective immune response. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|