The Studys On Anticancer Pharmacodynamics And Molecular Biological Mechanisms Of Extract Of Agaricus Blazei Murill

At present, cancers have still been one of the important factors in human death. The main treatment methodologies to tumors include operation,chemotherapy,radiotherapy, which in one side bring hopes and on the other side induce various injuries to patients. And the side effects of chemotherapy,radiotherapy are much bigger to postpone the recovery. Therefore high attention has been paid recently in the fields of biology and medine to select new drugs, especially natural medicines with higher efficiency, lower toxicity and low cost.Agaricus blazei murill is mycelium of fungi, which belongs to Basidiomycete and is originated from Brazil. The artificial cultivation of Agaricus blazei murill was established in 1978 at the Iwade Institute in Japan, and since 1988 Agaricus blazei murill has become widely cultivated in Japan and Indonesia. In recent years, many experts have isolated and purified steroids, polysaccharides, glycoprotein complex and nucleic acids from Agaricus blazei murill. Its effective components and pharmaceutical functions have been studied deeply, and it has been found that Agaricus blazei murill possesses the functions of anti-tumor, increase in immunity, anti-mutation, sterilization In 1995, Professor Liang Zheng in the Institutes for Botany, Chinese Academy of Sciences, successfully cultivated it with the grow wild strain from virgin forest in Brazil, and so it is named as Liang jing Mushroom. But the Agaricus blazei murill will be efficiency of anti-proliferation on what tumor, and what is the molecular mechanism? These questions will be necessary to make a thorough study.In order to investigate the anticancer effect and induction of apoptosis, of which we have isolated a novel type of RNA-protein complex (FA-2-b-β), a water-soluble polysaccharide extractive extracted from Agaricus blazei Murill. on tumor cells and its molecular mechanisms, the HL-60, MKN45 cell lines were used as target cells in vitro and these effects were assayed by microculture tetrazolium assays (MTT), flow cytometry assays, DNA agarose gel electrophoresis techanique, telomerase activity assays, the expression of caspase-3 assays, the expression of bcl-2 assays, transmission electronic microscopy technique. The corresponding results were gained as follows: 1. The RNA-protein complex (FA-2-b-β), a water-soluble polysaccharide extractive extracted from Agaricus blazei Murill, and AZT showed significant anti-proliferation effects in HL-60, MKN45 which obviously depended on time and dosage, and the obvious resistant rates in HL-60 was 82%(FA-2-b-β), rates in MKN45 was 49.44(FA-2-b-β), rates in MKN45 was 56.37%(AZT); 2. This research first indicated that the RNA-protein complex (FA-2-b-β), a water-soluble polysaccharide extractive extracted from Agaricus blazei Murill, and AZT treatment could significantly induce HL-60, MKN45 apoptosis in vitro. As the RNA-protein complex (FA-2-b-β) and AZT concentration increased, the G1 phase cell percentage increased while the S phase cell percentage decreased compared to the control. This may be an important molecular mechanism on inducing tumor cells apoptosis; 3. The research indicating that the RNA-protein complex (FA-2-b-β) and AZT treatment could significantly decreased the telomerase activity of HL-60, MKN45 in vitro. This also may be an important molecular mechanism on anti-proliferation of tumor cells; 4. The research also indicatied that the RNA-protein complex (FA-2-b-β) and AZT treatment upregulate the expression of Caspase-3 mRNA of HL-60, MKN45 cells in vitro. It may be an important molecular mechanism on inducing tumor cells apoptosis, changing cells cycle and anti-proliferation of tumor cells. 5. The research indicated that the AZT treatment could decrease the expression of bcl-2 protein of MKN45 in vitro. It may be an important molecular mechanism by which AZT induce apoptosis, change cell cycle and block the tumor cells at G1 phase. And it induce these cells apoptosis closely related to the changing of expression of bcl-2; 6. The research also the first indicated that combined treatment with both AZT and the RNA-protein complex (FA-2-b-β) and AZT showed better results than using any of them alone. And the synergy of AZT with FA-2-b-βcan be expected to be the new path towards the curement of gastric cancer.In conclusion, the RNA-protein complex (FA-2-b-β) of (extracted from Agricus blazei Murill) and AZT showed significant anti-proliferation effects in HL-60, MKN45. And it has obvious effects on inducing apoptosis of these tumor cells, blocking the proliferation. Meanwhile, it showed that the inducing apoptosis of tumor cells has close relation with changing of expression of bcl-2 and caspase-3,decreased the telomerase activity. The RNA protein compound, (extracted from Agricus blazei Murill), FA-2-b-β, itself has certain inhibition effect of cancer cell, and also has synergy effect to chemo-drugs(AZT), in addition, it can lessen the toxicity of the chemo-drugs(AZT). If combined with chemo-drugs(AZT), it may lead to a decrease of both the dose and toxity of chemo-drugs(AZT) without a reduce of their effects. For all the reasons above, as an aid to chemo-drugs(AZT), the exploitation of FA-2-b-βwill have clinical practice prospect.