[Synergistic role between rhIL-2 and adriamycin long circulating temperature-sensitive liposome in targeting therapy on tumor].
OBJECTIVE
To observe the synergistic role between rhIL-2 and adriamycin long circulating temperature-sensitive liposome (ALTSL) in targeting therapy of H22 tumor-bearing mice and explore their anti-tumor mechanism.


METHODS
The antitumor activity was evaluated by using the tumor's weight as an index. The prolongation rate of mouse life was calculated according to the survival time of the tumor-bearing mice. The killer activity of NK cells and the lymphocyte transformation rate were detected by the LDH and MTT colorimetry, respectively. The apoptosis of tumor cells and the expression of p53, Fas, Fas-L and Caspase-3 were analyzed by flow cytometry (FCM). The expression of IL-2 mRNA and IL-12 mRNA in splenocytes was determined by RT-PCR. The pathologic changes of tumor, heart, liver and kidney tissues of the tumor-bearing mice were observed under light microscope.


RESULTS
The tumoristatic rate of rhIL-2+ALTSL (73.5%) was higher than that of adriamycin liposome (ADML) group (67.0%). The survival time of tumor-bearing mice in ALTSL and rhIL-2+ALTSL groups was significantly extended as compared with the NS group (treated with normal saline) and the free ADM group (P <0.01 or P <0.05). The killer activities of NK cells of ALTSL group and rhIL-2+ALTSL group were higher than those of the NS and free ADM groups, and was highest in rhIL-2+ALTSL group. The lymphocyte transformation rate of ALTSL+rhIL-2 group markedly increased ( P <0.01) as compared with the free ADM group. The result of RT-PCR indicated that the expression of IL-2 mRNA and IL-12 mRNA in splenocytes in the adriamycin long circulating liposome (ALCL) group was significantly higher than that in the free ADM group. The enhancement of rhIL-2+ALTSL on expression of IL-2 mRNA and IL-12 mRNA was much stronger than that of ALTSL alone. The pathological examination indicated that in rhIL-2+ALTSL group, the tumor cells were mostly destroyed, and a large amount of lymphocytes and monocytes were found in tumor tissue.


CONCLUSIONS
ALTSL can increase the anti-tumor effect and decreased the side-effects (such as the cytotoxicity) of ADM. rhIL-2+ALTSL can induce the apoptosis of tumor cells and enhance killer activities of T cells and NK cells. rhIL-2 and ALTSL can synergistically play the antitumor effect.
Dong
Lan-feng
LF
Department of Laboratory Animal Sciences, Hebei Medical University, Shijiazhuang 050017, China. donglanfengcn@yahoo.com.cn
Mei
He-shan
HS
Song
Shu-xia
SX
Lu
Zhan-jun
ZJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001775:Blood Circulation; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D015996:Survival Rate; D013696:Temperature; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents; D007376:Interleukin-2; D008081:Liposomes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D018664:Interleukin-12; D004317:Doxorubicin