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Study On Anti-Cervical Cancer And Immunomodulating Effects Of Sub-Fraction 1a Of Polysaccharides From Solanum Nigrum Linne

Posted on:2010-09-10Degree:DoctorType:Dissertation
Country:ChinaCandidate:J LiFull Text:PDF
GTID:1114360302959221Subject:Applied Chemistry
Abstract/Summary:PDF Full Text Request
Uterine cervical carcinoma is one of the most common gynecologic malignant tumors in the world, and its occurrence ratio has taken the first place in the developing countries. Because it has the trend of rejuvenation in cervical cancer emergence, and the rate of cervical adenocarcinoma is increasing, find a feasible method to enhance the efficacy of radiotherapy and chemotherapy becomes increasingly attractive. Recently, natural-derived antitumor agents have attracted more attention for less side effects and no-drug-resistance.Solanum nigrum Linne is a kind of traditional Chinese medicine, and it has the effects of antibacteria, antivirus and antitumor. Polysaccharides of Solanum nigrum L. (SNL-P) was got by water-extraction and alcohol precipitation, and a sub-fraction 1a (SNL-P1a) was got through further purification which was homogeneous in molecular weight and stable in quality. After the cervical cancer-bearing mice models were established, the effects of SNL-P1a on body's immune system, antioxidant defense system, cell cycle and apoptosis of tumor tissue cells were studied by methods of flow cytometry, immunohistochemistry, enzyme linked immunosorbent assay (ELISA), transmission electron microscopy (TEM) and reverse transcription-polymerase chain reaction (RT-PCR).After oral administrated tumor-bearing models with SNL-P1a for 13 days, the growth of solid tumor was inhibited significantly (P<0.05). The weight inhibition rate was 37.65 and 52.52%, and the volume inhibition rate was 36.75 and 50.19% for low and high dose treatment, respectively. SNL-P1a inhibited the growth of ascites tumor (P<0.01), and the inhibition rate was 40.00 and 53.68% for low and high dose treatment. It also prolonged the survival time of tumor–bearing mice (P<0.05, P<0.01), and the life span increasing rate was 43.95 and 76.43% respectively. Furthermore, it inhibited the lung metastasis of uterine cervical cancer (P<0.05, P<0.01), and the inhibition rate was 38.92 and 53.89%, respectively.SNL-P1a treatment enhanced the thymus weight of tumor-bearing mice (P<0.05), and the thymus index increasing rate was 220.11 and 179.89% for low and high dose respectively. SNL-P1a could ameliorate the atrophy, structure destruction and cell apoptosis of thymus tissue caused by tumor onslaught by elevating Bcl-2/Bax ratio and further repressing cell apoptosis. But the protection effect of SNL-P1a on spleen tissue was not significant.SNL-P1a treatment could increase the proportion of peripheral blood CD4+ T lymphocyte subpopulation and decrease the proportion of CD8+ T lymphocyte subpopulation significantly (P<0.01), so ameliorate the reversion status of CD4+/CD8+ of tumor-bearng mice. It could also up-regulate the levels of serum IFN-γand IL-2, but down-regulate the level of serum IL-4 (P<0.01, P<0.05), then reverse the shift of Th1/Th2 toward Th2 partially. Meanwhile, SNL-P1a treatment could also decrease the level of serum TNF-αsignificantly, which deprived the necessary conditions of the growth and metastasis of tumor cells.SNL-P1a treatment could increase the levels of serum T-SOD and T-AOC (P<0.05, P<0.01), but decrease the MDA level in tumor-bearing mice significantly (P<0.05). It also improved the T-SOD and T-AOC levels in liver and kidney of tumor-bearing mice, and improved the GR level in liver but did not influence the GR level in kidney (P>0.05). Furthermore, SNL-P1a could increase the T-AOC level in thymus and spleen tissue (P<0.05, P<0.01), increase T-SOD level in thymus (P<0.05), but not in spleen (P>0.05). It could also enhance GR level in thymus and spleen tissues. To tumor tissues, SNL-P1a treatment decreased T-AOC, T-SOD and GR levels significantly (P<0.01). Besides that, the serum LDH level of tumor-bearing mice was suppressed by the treatment of SNL-P1a markedly (P<0.01), but the serum AKP level remained unchanged (P>0.05). Experiments in vitro further showed that SNL-P1a had strong effects on scavenging·OH radical, O2·- radical and DPPH radical.The tumor cell cycle was arrested in G2/M phase by SNL-P1a treatment, which might cause by the down-regulation of proteins of proliferating cell nuclear antigen (PCNA), c-myc, mutant p53 and cyclinD1 and the up-regulation of protein p21. Meanwhile, SNL-P1a treatment also caused the up-regulation of proteins Fas, FasL, Bax and Caspase-3 and down-regulation of Bcl-2 protein in tumor tissue cells, which might lead to the apoptosis of tumor tissue cells.The studies of anti-cervical cancer and immunomodulating effects of SNL-P1a on tumor-bearing mice provided theoretical supports for further development of SNL-P1a as an anti-cervical cancer agent.
Keywords/Search Tags:Sub-fraction 1a of polysaccharides from Solanum nigrum L., Cervical cancer, Immunomodulating, Antioxidant, Cell apoptosis
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