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Study On Molecular Biology Mechanism Of Anti-tumor Compounds

Posted on:2005-09-16Degree:MasterType:Thesis
Country:ChinaCandidate:J ChenFull Text:PDF
GTID:2144360125950321Subject:Microbial and Biochemical Pharmacy
Abstract/Summary:PDF Full Text Request
The advancement of tumor prevention and treament has closerelation with the derection of medicine of high anti-tumor. As theresult of chemistry combination with pharmacology andbiochemistry, people has found much more new compounds that candamage the tumor cell. More energy pay to the natural products thatcome from plants. Nowadays, there are many ways that thosenatural products damage tumor cells, but people pay moreattentions to the natural products that can induce tumor cells toapoptosis. With the advancement of more information on molecularondology people has gained more and more insights into theoccurrence and development of tumor. This knowledge provides thenew nose and target for studies on anti-tumor drug and cancertherapy. This paper selected one perylenequinone compound thatcan induce tumor cells to apoptosis, that is HypocrellinA.HypocrellinA can induce many tumor cell including HeLa,A375-S2,Hce-8693 and S-180 to apoptotic alike morphosis change, andinduce DNA to 180bp times DNA ladder.This paper also discussedthe molecular mechnism, studied HypocrellinA induce mRNAchanges of HeLa cell relarive apoptotic regulators (Bax, Bcl-2),studied the association between the mRNA changes of HeLa cellrelative cell cycle regulators and the changes of HeLa cell cycle.The results show that mRNA of Bax will increase with theincreasing of dealing time, while mRNA of Bcl-2 will decrease.Because the active of Bax can induce cell to apoptosis, while Bcl-2determin the suivive of cell, so our experiment can can certify thatonce cell apoptosis, mRNA of Bax will increase and mRNA of Bcl-2will decrease; the cells of p21disfounction will result that cellpassed G1-phase without any restriction, while active p53 will leadto cell cycle arresting. The results of RT-PCT show that mRNA ofp53 increase, while mRNA of p21 decrease then increase , and theresults of Flow Cytometer show that HeLa cells accumulated inS-phase in one cell cycle. Because wether mRNA of p53 andcyclinB1 is normal or not will derectly determin the change of cellcycle. So we can make tentative conclusion that mRNA of p53increase, mRNA of p21 decrease and mRNA of cyclinB1 decreaseresult in the change of HeLa cell cycle, accumulating of most cellsin S-phase damage the cell cycle, just because of the changes ofthose cause HeLa cell to apoptosis. We researched relationshipbetween several drugs (including HypocrellinA, 5Fu and SWI) andthe changes of A375-S2 cell cycle and mRNA of A375-S2 cell cyclerelative regulators, the results show that those compound all canresult that A375-S2 cell cycle change, S-phase cell accumulate, andmRNA of cyclinB1 increase, which demonstrate that compound thatcan induce tumor cell to apoptosis can lead to the change of cellcycle, then following the mRNA change of cyclinB1, therefore weconclude that cyclinB1 may be used as a target of anti-tumor drugsscreening.
Keywords/Search Tags:Anti-tumor
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