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The Effect Observation of Sorafenib in Combination with OXA Contribution to HCC Bel-7402 and the Investigation of Some Resistant Related Proteins

Author: WuYan
Tutor: ZhangYang
School: Dalian Medical University
Course: Oncology
Keywords: Sorafenib OXA Pgp ABCG2
CLC: R735.7
Type: Master's thesis
Year: 2008
Downloads: 183
Quote: 2
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Abstract


Background and purpose: Hepatoma primarily is one of most common malignant with threat in the human existence, disease rate is stepping up in recent years. Both traditional chemotherapy and transcatheter arte-rial chemoembolization are comon processes in the unoperational therapy of HCC .But they are satisfactory in the prostecdtive efficacy. The targeted therapy as a extraordinary potential therapy,has been one part of clinical thrapy in Hepotacellula carcinoma.Sorafenib is a ultramodern multikinase inhibitor for oral use. Sorafenib inhibited not only the proliferation of tumor cell but also the shape of tumor vessel,which inhibited the tumor cell metastasis .From the dates of clinical application and laboratory research, it is a potential agent because its good curative effect and tolerated adverse effect..SHARP trial displayed that sorafenib improved OS by 44%,sorafenib is the first therapeutic drug which extended markedly the OS in HCC patients.Oxaliplatin as the third era platinum drug,preclinical study confirmed that oxaliplatin had a good effect on HCC.Empirical study certificated that both of them had no impact in pharmacokinetics.The object of this study is to invest the foundational research how OXA(the conventionalchemotherapy)to go with Sorafenib to kill thetumor cell with flow cytometer and to study whether Pgp ,ABCG2 are involved in the resistance of BEL-7402/sorafenib by western blot.Methods: The object of this study is the BEL-7402,human cell,hepotacellula carcinoma,with differerent administration sequence of sorafenib and OXA.The purpose is to observe the which way will kill the tumor cell to the great extent.The cell BEL-7402/sorafenib, BEL-7402/OXA, BEL-7402/ sorafenib- OXA, BEL-7402/ OXA- sorafenibwere evaluated with the MTT assay which measures mitochondrial activity and to determine the concentration reguired for 50 inhibition of growth; Cell morphologic change and cell ultrastructural change aie observed by the electron microscope; Flow cytometer detects and analysis the cell cycle change and cell apoptotic change;Besides,we use western blot to check the variance of the two proteins in order to find which one plays a role in the resistance process .in thebel-7402/sorafenib.The resistant proteins include:Pgp and ABCG2.Results:1.the concentration reguired for 50 inhibition of BEL-7402/OXA growth is 5-15.35ug/mL,and the concentration required for 50 inhibition of BEL-7402/sorafenib growth is 2.17-8ug/mL.Both of them are less than 20ug/mL.2.The result of flow cytometer exhibited that OXA prevented the generation of Bel-7402 affected by OXA, the cell cycles of S stage,G2 stage and M stage are arrested and the rate of apoptosis achieved 19.39%;sorafenib also prevented the generation of Bel-7402 affected by sorafenib all the more and the rate of apoptosis achieved 25.66%;Besides, both OXA and sorafenib prevented the generation of BEL-7402 affected by OXA+sorafenib and the rate of apoptosis achieved 38.54%;both sorafenib and OXA prevented the cell generation of BEL-7402 affected by sorafenib and OXA and the rate of apoptosis achieved 31.32% exclusively.3.The volume of BEL-7402 cell affected by sorafenib and OXA respectively deflated,growed round, cytoplasm concentrated , caryon pyknosised and anachromasised ; and the BEL-7402 cell morphous dispayed the nonage of apoptosis with electron microscope.4.Western blot displayed that ABCG2 is detected in the BEL-7402 not only with interval hymodensitivel sorafenib but also continuing hypodensitive sorafnib,and ABCG2 hymoexpressed in the section of continuing hypodensitive sorafnib compared with the section of continuing hypodensitive sorafnib.but the expression of Pgp has not changed.Conclusion:1.BEL-7402 cell is hypersensitive to sorafenib and OXA respectively.Both of them have synergistic effect on HCC BEL-7402,; besides,OXA firstly and sorafenib secondly achieved the better effect.2.BEL-7402 cell which is affected by continuing hypodensitive sorafenib generated the drug-resistance more easy in vitro.3.The drug-resistance of BEL-7402 cell is affected by sorafenib is corralated with the high expresstion in ABCG2; Pgp has nothing to do with this process possibly.

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CLC: > Medicine, health > Oncology > Gastrointestinal Cancer > Liver tumors
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