Anti-tumor And Anti-radiation Effects Of The Compound Polysaccharide And Their Mechanisms

Cancer is the first cause of death among the adult population. The strategiesemployed in clinical practice are to remove the tumor through operation which isfollowed by chemotherapy. The disadvantages of chemotherapy are that theirspecificity is not satisfying and lymphocytes which play pivotal role in fightingtumors are destroyed. Moreover, immunosuppression is detected in patients withcancers. Therefore, how to improve immune response of cancer patients is critical incancer treatment. Substantial studies report that polysaccharides haveimmunomodulatory or antitumor activities. Reports show that polysaccharides fromdifferent herbs have different activities. Thus, we hypothesize that combination ofpolysaccharides from different herbs will produce better efficacy in inhibiting tumorcell growth and antagonize radiation damage.Part Ⅰ The anti-tumor effects of the mixture of three polysaccharideMTT assay results show that PLE, PTM and PG can produce no significanteffects on the growth of B16and H22cells, which suggest that PLE, PTM and PG donot have the capacities to kill tumor cells, and PLE and PTM can produce effects onthe growth lymphocytes. CTL activity was determined by lactate dehydrogenase(LDH) release assay. The results showed that PLE, PTM and PG were able toincrease the activities of CTL. The dosage proportions of mixture of threepolysaccharides were optimized by orthogonal test.Mice were injected with H22or B16cell and then treated by chemotherapydrugs (5-fluorouracil or cyclophosphamide), mixture of polysaccharides (PM), orchemotherapy drugs+PM. The tumor weight, tumor volume, the subgroups of CD4+and CD8+in spleen, the natural killer (NK) cell and cytotoxic T lymphocyte (CTL)activities of splenocytes and the levels of Tumor Necrosis Factor-α (TNF-α),Interleukin-2(IL-2), Interleukin-4(IL-4), and Interferon-γ (IFN-γ) were determined. Compared with mice from model, chemotherapy drugs, PM groups, the mice treatedwith chemotherapy drugs+PM showed: significantly smaller of tumor weight andvolume. Compared with mice from chemotherapy drugs, the mice treated with PMand chemotherapy drugs+PM showed:(1) significantly increased NK and CTLactivities of splenocytes;(2) significantly increased subgroups of CD4+and CD8+inspleen (3) signficantly higher levels of TNF-α, IL-2, and IFN-γ in serum;(4)significantly lower levels of IL-4in serum; Combination of polysaccharides fromlentinus edodes, tricholoma matsutake and ginseng can help chemotherapy drugsproduce more effective inhibition of H22and B16cell growth. One of themechanisms by which PM strengthened the efficacy of chemotherapy drugs ininhibiting H22and B16cells growth was that PM can increase the activities of NKand CTL. Another mechanism through which PM helped inhibit cancer cell growth isthat they can stimulate the secretion of cytokines related to tumor cell death. Theother mechanism that PM enhanced chemotherapy drugs inhibiting H22and B16cells growth was that PM can increase the percentage of subgroups of CD4+andCD8+.Part Ⅱ The anti-radiation effects of the mixture of three polysaccharideEstablish γ-ray radiation damage models of mice and observe the anti-radiationeffects of PM. The mice were divided randomly into five groups: Normal controlgroup (NC), Irradiation control group (IC), Low-dose PM group (PML),Medium-dose PM group (PMM), High-dose PM group (PMH). PM was administeredto the mice for14days. After the14days, the mice in all groups were irradiated with4Gy γ-ray except NC group. The spleen index, thymus index, the prolife reaction ofsplenocytes to ConA, white blood cell count, the content of bone marrow DNA, the number ofnucleated bone marrow cells, the micronucleus rate of bonemarrow polychromatic erythrocyte,MDA content, SOD activity, CAT activity and GSH-Px activity were determined in1st,3rd,7thday after radiation. Compared with mice from IC group, the mice treatedwith PM showed:(1) significantly increased spleen index, thymus index and the prolifereaction of splenocytes to ConA;(2) significantly increased white blood cell count, thecontent of bone marrow DNA and the number of nucleated bone marrow cells;(3) significantly decreased the micronucleus rate of bone marrow polychromaticerythrocyte;(4) significantly increased SOD activity, CAT and GSH-Px activities inserum;(5) signficantly decreased MDA content in serum. PM had strong anti-γ-rayradiation activity.Part Ⅲ Toxicological studies of the mixture of three polysaccharideThe toxicity of PM was determined by maximum tolerance experiment and bonemarrow micronucleus test. The maximum tolerance test results showed: maximumtolerance dose (MTD)>30g/kg·BW. Micronucleus test in mice showed that therewere no significant differences between the PM group and the negative group. PMwas non-toxic and did not induce the micronuclear rates.In conclusion, combination of polysaccharides from PLE, PTM and PG werenon-toxic and can help produce a better efficacy of tumor inhibition together withchemotherapy drugs. PM can antagonize the adverse effects, such as the low functionalimmune status, oxidative and hematopoietic system damage, caused by γ-ray radiation.