[Antitumoral efficacy by systemic delivery of cationic liposome-plasmid interleukin-15 complexes in murine models of lung metastasis].
OBJECTIVE
To investigate the therapeutic effect of the plasmid pcDNA3.1-IL15 complexed with cationic liposome (CL-IL15) in the B16-F10 melanoma lung metastasis model.


METHODS
A plasmid with high secretive efficiency of IL-15 was constructed and the optimum mix ratio was determined to formulate cationic liposome-plasmid complex with the optimal encapsulation. The CHO-K1 cell line was transfected by CL-IL15. The secretion of transfected IL-15 gene was detected by Western blot and its biological function was measured through the proliferation response of CTLL-2 cytotoxic T cell line of murine by MTT assay. The C57BL/6 mice were inoculated intravenously (i.v.) with B16-F10 melanoma lung metastasis cells then treated (i.v.) by CL-IL15 in a therapeutic setting to determine the tumorigenesis and research the corresponding mechanisms.


RESULTS
The pcDNA3.1-IL15 plasmid was successfully constructed and the mass-ratio of optimal condition of cationic liposome-plasmid with perfect entrapment was 1:5 (plasmid: cationic liposome). Western blot analysis displayed the detection of IL-15 both in the medium and the pcDNA3.1-IL15 transfected cells. MTT assay showed that CTLL-2 cells could proliferate with the medium obtained from CHO-K1 cells transfected by CL-IL15. And the administration of CL-IL15 complexes led to the significant inhibition lung metastasis of malignant melanoma (P<0.05).


CONCLUSIONS
CL-IL15 could inhibit the metastasis of malignant melanoma and the cationic liposome delivered plasmid pcDNA3.1-IL-15 complexes may be an efficient therapeutic strategy for the treating of lung metastasis. And the effective splenic cell-mediated cytotoxicity and the obvious NK cells recruitment may be involved.
West China Hospital of Sichuan University, Chengdu, China.
Xiu
X
Teng
Xi-kun
XK
Zhou
Yin-bing
YB
Zhang
Ji
J
Qiu
Yong-qiu
YQ
Mao
Hong-xin
HX
Deng
Jiong
J
Li
D000818:Animals; D016466:CHO Cells; D002412:Cations; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004195:Disease Models, Animal; D015316:Genetic Therapy; D019409:Interleukin-15 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D008081:Liposomes; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology / Q000556:secondary* / Q000628:therapy*; D008546:Melanoma, Experimental / Q000556:secondary / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics*
D002412:Cations; D019409:Interleukin-15; D008081:Liposomes