Association Analysis On Mmp-3 Polymorphism And Breast Cancer And Anti-tumor Mechanism Study On Long-quan Compound Traditional Chinese Medicine

The researches include two parts, one is association analysis on MMP-3 polymorphism and breast cancer, the other is anti-tumor mechanism study on Long-Quan Compound Chinese Traditional Medicine. They would be summarized respectively as following.1. Breast cancer is one of the most common malignant tumors of women in the world. MMP-3 which can degrade extracellular matrix has recently emerged as an interesting candidate for a mammary tumor accelerator that may also influence tumor initiation and modify breast cancer risk. We want to investigate if single nucleotide polymorphisms (SNPs) in MMP-3 gene are associated with susceptibility to breast cancer. In this case-control study, we genotyped three SNPs in MMP-3 gene by PCR-RFLP in a well-characterized breast cancer series of 195 cases and 235 controls from Chinese Han population in Wuhan. The three SNPs are -1171 5A/6A site in promoter region, rs679620(Lys45Glu) in exon₂ and rs41357345(Arg248Trp) in exon₅ respectively. The results show that, there is no T allele of rs41357345 appeared in all samples, and the frequencies of 1171 5A/6A and rs679620 in case and control group are all consistent with Hardy-Weinberg equilibrium but no obvious difference was found in this two groups on the two sites respectively(P>0.05). -1171 5A/6A and rs679620 are not Linkage equilibrium (D'=0.763,r2=0.187). There is no significant difference on haplotype frequencies of two-SNP between case and control (Global P=0.747). But 6A_A haplotype frequency of case group(0.216) is less than control(0.230), while 6A represent a weaker promoter and A allele of rs679620 is benefit for apoptosis induced by MMP-3. 6A_A haplotype could be a protective element of breast cancer. There are no substantial evidences to support the association between SNPs in MMP-3 gene and susceptibility to breast cancer, but the trend that 6A_A haplotype could be a protective element to cancer development and progression was found. More SNP sites in MMP-3 should be selected and the samples mass should be amplified to carry out much deeper research on association between MMP-3 gene and susceptibility to breast cancer. 2. Long-Quan compound traditional Chinese medicine was an efficient prescription to treat varieties of cancers. Long-Quan medicine includes nine Chinese herbs, such as Semen Strychni, Indian Iphigenia Bulb, Fructus Camptothecae Acuminatae, Solanum nigrum Linn, Astragalus membranaceus, Selaginella doederleinii Hieron, Ganoderma Lucidum, Natural Indigo and Tatarian Aster Root respectively. We are going to study the anti-tumor mechanism of Long-Quan medicine. In this study, natural pharmaceutical chemistry and medicine antiserum pharcology were used respectively. Alkaloids extracted from Indian Iphigenia Bulb, Fructus Camptothecae Acuminatae, Solanum nigrum Linn and Tatarian Aster Root show remarkable anti-tumor activity in votro respectively, but alkaloids extracted from Long-Quan compound medicine by acetate put up low inhibition ratio on EC-1 cells growth. Using rabbits as experimental animals to prepare antiserum of Long-Quan compound medicine, the antiserum of Long-Quan compound show shtronger anti-tumor effection. In conclusion, alkaloid is an effective component for anti-tumor, and the reasons for why alkaloid extracted from Long-Quan compound has a weak anti-tumor, it may because it happens many unknown chemical reaction in preparation process which reduce the activity of active ingredients. Chinese medicine serum simulate the process of absorption of compound traditional Chinese medicine, In vitro experiments shows that some parts of anti-tumor drugs can kill tumor cells directly, but the more important is that when Long-Quan compound absorbed by human body, it can produce a variety of molecules or proteins that has stronger anti-tumor. The further researches were needed to make clear the molecules or proteins induced by Long-Quan compound.