| Objective: The pharmacological effect on antineoplastic of traditional Chinese medicine mainly including strengthening body resistance (immunoloregulation), eliminating pathogen (antineoplastic), attenuation(cutting down the side effect of chemotherapeutics) and synergism (elevate the curative effect of chemotherapeutics). The synergic effect is very important about the feature of traditional Chinese medicine's antineoplastic. Stichopus japonicus acid mucopolysaccharide (SJAMP) is a kind of acid polysaccharide extracted from Stichopus japonicus Selenka, it has antineoplastic, antimetastatic, anti-rumor angiogenesis, immunoloregulation, anti-cogulation and other bioactivities. The previous studies showed that SJAMP had synergic effect to cyclophosphamide(Cy) , and this study will certify the synergism on other anti-tumor chemotherapeutics on the basic of this effect on Cy, then infer whether it has the wide synergic effect, and primarily study its mechanism.Methods: The evaluation of synergic effect on antineoplastic of SJAMP was designed according to《The investigation on pharmacodynamics of Chinese traditional medicine of therapy malignant tumor》in《Guide of investigation of new drug of Chinese traditional medicine》. Hep A of mice was selected as tumor model, and Cy, 5-Fu and DDP were selected as chemotherapeutics. Three dose (high, middle, low) groups of chemotherapeutant and two (middle and low) dose groups combined with SJAMP and SJAMP-single group were designed in the experiments. Prepared Hep A cells suspension, s.c in right armpit of mice, administrated these medicine the next day, Every medicine's dose is : Cy 80mg/kg,40mg/kg,20mg/kg, qd×1; 5-Fu 40mg/Kg,25mg/Kg,15mg/Kg, qd×4 ; DDP 2mg/Kg ( qd×2 ) , 2mg/Kg(qd×1), lmg/Kg(qd×1); SJAMP100mg/Kg im qd×l. Mice were sacrificed after 7 days and tumor tissues were got, weight the tumors, and then calculated the inhibitory rate of tumor growth. The effect of SJAMP on tumor cell's proliferation in vitro was measured by MTT assay, then observed the effect of SJAMP and SJAMP in serum combined with chemotherapeutics on Hep A tumor cell in the same way. To study the effect of SJAMP on drug concentration in tumor tissue was assayed by HPLC. Statistics method is ONE-WAY ANOVA or /-test, CDI and Q methods were used in evaluation of synergic experiments.Results: In vivo , SJAMP has very significant effect on synergism to DDP, 5-Fu and Cy. There was significant effect on the average weight of tumor of three dose of Cy single group, and middle, low dose combinative groups (P＜0.01), The evaluation of middle dose combinative group is CDI=0.42, Q=1.18, and the evaluation of low dose combinative group is CDI=0.70, Q=1.51.The same results were found in DDP experiment group, CDI=1.09, Q=0.90(middle dose combinational group), CDI=1.01, Q=0.98 (low dose combinative group). That's of 5-Fu experiment group is: CDI=0.75, Q=1.19(middle dose combinative group), CDI=0.98, Q=1.03(low dose combinative group). In vitro , there was no significant cytotoxic effect of SJAMP single used to four kinds of tumor cells; there was synergic effect when SJAMP combined with DDP, and this effect could not be found in combined with 5-Fu and Cy, but the synergic effect could be found when SJAMP contained in serum. There was lower concentration of 5-Fu when SJAMP combined with 5-Fu than 5-Fu single treated group(11.51%), but there was no significant in statistics, P＞0.05.Conclusion: There was very well synergic effect on DDP, Cy and 5-Fu in vivo, and no cytotoxic effect on tumor cells when SJAMP single treated group in vitro, and there was no significant synergic effect combined with chemotherapeutics, but there was very well synergic effect of SJAMP contained in serum. All the results show that the antineoplastic and synergism of SJAMP only could be found when it was metabolized after absorbed in blood. |
