| Objective:Total glucosides of paeonia (TGP) is from the effective parts of dry white paeony root, the main effective components include paeoniflorin, hydroxy paeoniflorin, peony lactone glycosides, benzoyl paeoniflorin, etc., of which the content of paeoniflorin is the highest and over 90%.Liposome of total glucosides of paeonia (TGP Liposome) is composed of liposomes with TGP, which could increase the stability of the drug, increase the liver targeting effect, improve drug bioavailability greatly. This study is explore the effects of TGP Liposome antitumor activity in vitro and in vivo, the effects of tumor growth and immune function in tumor-bearing mice, which can provide scientific experimental basis for the clinical application of malignancy with TGP Liposome, and seeking a safe and effective new Chinese traditional medicine to tumor treatment.Methods:1. The effects of TGP Liposome on antitumor activity in vitro:K562, SMMC-7721, BEL-7402, HCT116 and KB cell lines were cultivated, TGP Liposome were diluted with saline water in 6.25, 12.5,25,50,100, and 200 μ.g.mL-1, The effects of TGP Liposome on antitumor activity in vitro were detected by CCK 8 kits (Cell Counting Kit-8).2. The effects of TGP Liposome on antitumor activity in vivo:H22 solid tumor strains (S), H22 ascites tumor (type A) and S180 sarcoma cells were cultivated in mice to establish the mice tumor model of liver cancer H22 solid tumor type (S), H22 ascites tumor (type A) and mice portability sarcoma,TGP Liposome were administrated with 50,100,200 mg·Kg-1, positive control group were intraperitoneal injection by of DDP1 mg·Kg-1, negative control group were lavaged with saline, all group were administrated once a day, and last 14 days.The tumor growth, tumor weigh,thymus and spleen weight, the thymus index and spleen index, and the tumor inhibitory rate were detected on H22 solid tumor type (S) mice and sarcoma mice.the rate of life extension were observed on H22 ascitic fluid tumor (type A) mice, the antineoplastic activity of radix paeoniae alba total glycosides liposomes were evaluated on H22 ascites tumor (type A) mice3. The effects of TGP Liposome on the immune ability of mice:To detect The effects of TGP Liposome on the ability of cavity macrophage in mice 200 macrophages (M 0) were counted by oil microscopic to calculate the percentage and index of macrophage cell.To detect The effects of TGP Liposome on the lymphocyte transformation reaction induced by ConA,PI were calculated.The express of IL-2, IL-12 and TNF-a were detected by Western blot.Results:1. The effects of TGP Liposome on antitumor activity in vitro:TGP Liposome significantly inhibited proliferation of K562, SMMC-7721, BeL-7402 cells with IC50 values of (29.69±3.72), (62.49±4.97) and(67.55±8.33) μg.mL-1 respectively.It showed a favourable dose-effect relationship becasue Inhibitory activity strengthened with the increase of concentration. However inhibitory effects on HCT116 and KB was too weak.Compared with negative control group,50,100 and 200 mg.kg-1 TGP Liposome group increased the weight of mice was no significant (P> 0.05).Compared with negative control group,DDP (1 mg·kg-1) group inhibited the tumor growth significantly (P<0.01); Compared with TGP Liposome groups, the weight, spleen index and thymus index of mice on DDP (1 mg·kg-1) group were decreased significantly (P<0.01 or significantly (P< 0.01).The effects of TGP Liposome on antitumor activity in vivo:The 50,100 and 200 mg.kg-1 TGP Liposome group present antitumor rate of 25.53%,41.96 % and 49.22% on mice hepatomaH22 cells solid tumors(Type S) respectively; The tumor inhibition rate of 50,100 and 200mg.kg-1 TGP Liposome on mice S180 tumors was 33.51%,47.03% and 57.83% respectively and TGP Liposome could increased the spleen index and thymus index on mice with S180 tumors;Compared with negative control group, the difference shows statistical significance (P<0.01 or P<0.05). Life extension rate of 50,100 and 200 mg.kg-1 TGP Liposome on H22 ascites tumors (Type A) mice was 26.10%, 45.92% and 61.60% respectively, Compared with negative control group, the difference shows statistical significance (P<0.01 or P<0.05)3.The effects of TGP Liposome on the immune ability of mice:Compared with negative control group,three TGP Liposome groups can increased the The index of macrophage cell in abdominal cavity and Phagocyte rate significantly(P< 0.01) compared with TGP Liposome groups, DDP group can decreased the The index of macrophage cell in abdominal cavity and Phagocyte rate significantly(P< 0.01 or P<0.05).Compared with negative control group,100,200 mg·Kg-1 TGP Liposome groups which administrated TGP Liposome 10 days could increased the Splenic lymphocyte reaction on mice significantly (P<0.01). Compared with TGP Liposome groups, DDP group can decreased the Splenic lymphocyte reaction on mice significantly(P<0.01 or P<0.05). compared with negative control group, TGP Liposome could increased the expression of IL-2,IL-12 and TNF-a_significantly(P<0.01). Conclusion (1) TGP Liposome inhibited proliferation of K562, SMMC-7721, BeL-7402 significantly,while the inhibitory actions to HCT116 and KB was weak,so TGP have antitumor activity in vitro definitely.(2) TGP Liposome can inhibited the growth of H22 solid tumor type (S) and S180, extend the survival time of the H22 ascites tumor (type A) mice, which mechanism may be related to enhance the function of macrophage phagocytosis on tumor-burdened mice abdominal cavity, promoting the transformation of lymphocyte reaction, increased the expression of IL-2, IL-12 and TNF-alpha on tumor-burdened mice. |
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