[Anti-tumor effect of monkshood polysaccharide with adriamycin long circulating temperature-sensitive liposome and its mechanism].
OBJECTIVE
To observe the synergic action of monkshood polysaccharide (MPS) and adriamycin (ADM) long circulating temperature-sensitive liposome (ALTSL) in targeting therapy for H22 tumor-bearing mice and explore the mechanism.


METHODS
The anti-tumor activity was evaluated by using the tumor's weight as an index. The life prolongation rate of mice 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 release assay and MTT colorimetry, respectively. The apoptosis of tumor cells and the expressions of p53, Fas, Fas-L and caspase-3 were analyzed by flow cytometry. The expressions of IL-2 mRNA and IL-12 mRNA in spleen lymphocytes were 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
Compared with the adriamycin liposome group, the anti-tumor effects were enhanced in (MPS+ALTSL) group with tumor growth inhibitory rate up to 80.4%. The survival time of the tumor-bearing mice in ALTSL and (MPS+ALTSL) groups was significantly prolonged compared with the ADM group (P<0.01). The killer activity of NK cells was higher in ALTSL group than in the NS and ADM groups, and was highest in (MPS+ALTSL) group. The lymphocyte transformation rate of (MPS+ALTSL) group was markedly increased (P<0.01) as compared with the ADM group. The result of RT-PCR indicated that the expressions of IL-2 mRNA and IL-12 mRNA in lymphocytes in the adriamycin long circulating liposome (ALCL) group were significantly higher than those in the ADM group. Expressions of IL-2 mRNA and IL-12 mRNA was much higher in (MPS+ALTSL) group than in ALTSL group. The pathological examination indicated that in (MPS+ALTSL) group, more lymphocytes and monocytes were found in tumor tissue.


CONCLUSIONS
ALTSL can increase the anti-tumor effect and decrease the side-effects (such as the cytotoxicity) of ADM. MPS combined with ALTSL can enhance killer activity of NK cells and transformation of T cells, supporting their synergic anti-tumor effect.
Dong
Lan-feng
LF
Experiment Animal Department, Hebei Medical University, Shijiazhuang 050017, China.
Zhang
Ying-jun
YJ
Liu
Jing-sheng
JS
Song
Shu-xia
SX
Hou
Jie
J
Lu
Zhan-jun
ZJ
D031841:Aconitum / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018664:Interleukin-12 / Q000235:genetics; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008081:Liposomes / Q000097:blood* / Q000737:chemistry*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000473:pathology; D011134:Polysaccharides / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D013696:Temperature; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents; D008081:Liposomes; D011134:Polysaccharides; D012333:RNA, Messenger; D018664:Interleukin-12; D004317:Doxorubicin