| Background:In clinical practice we discovered that after the chemotherapy which directlyaimed at the solid tumor, the tumor was clinical extinctted. However it would recursoon. The reason should be that the traditional therapy didn't eradicate the tumorcells thoroughly but just diminish the quantity of tumor cells and reduce the volumeof the tumor. The very few tumor cells which were survived would make the tumorrecur. The infiltration, metaptosis and recurrence of malignant tumor gave us a hintthat there is a kind of cells which have the boundless reproductive activity. Thecancer stem cell hypothesis implicate that tumor origin from the stem cells, to say inother words, oncology is a disease of stem cells. This new concept of cancer is a hugechallenge to the traditional cancer treatments, and therapy targeted to cancer stemcell could indeed be a shining light on the cancer research horizon. Primary hepaticcarcinoma (PHC) is a kind of solid tumor which is hard to cure. We need separatedthe subpopulation cells like the tumor stem cells from PHC and studied the biologycharacteristic of these subpopulation cells. So we can do susceptibility test whichaim to the TSC to make a precise individualization chemotherapy. It is a usual wayto do susceptibility test by culturing tumor cells in vitro. But it is hard for us toseparate the TSC from solid tumor. Fortunately we found out that tumor stem cells origin from the correspondence normal stem cells. We also found out that the tumorstem cells in PHC must be origin from oval cells which come from bone marrowstem cells (MSCs or HSCs) which are easy to separate. According to this theory westudy whether MSCs can be used to take the place of tumor stem cells in PHC foranticancer drug sensitiveness evaluation in vitro.Objective: To study the correlation of anticancer drugs sensitivity betweenhepatocarcinoma cells and MSCs (marrow mesenchymal stem cells) in rats andwhether MSCs can be used to take the place of tumor stem cells in PHC foranticancer drug sensitiveness evaluation in vitro.Methods: The primary liver carcinoma was induced by 0.025% diethylnitrosaminein rats. Tumor cells and MSCs were separated from 10 hepatocarcinoma rats. thecell surface marker CD29,CD34,CD44,CD45 were tested by flow cytometry. Theinhibition ratio of Epirubicin,5-Fliorouracil. Gemcitabine. Cyclophosphamide andCisplatin to hepatocarcinoma cells and MSCs were measured by SRB way after 24hours. The weight of the tumor in nude mice, which were injected rats'hepatocarcinoma cells treated by anticancer drugs, was measured after 6 weeks.Then the differences of drugsensitivity between hepatocarcinoma cells and MSCsand the correlation of the inhibition ratios of anticancer drug to the weight of thetumor in nude mice were analyzed.Result:一(1)18 rats were induced hepatocarcinoma in 30 rats. (2)The tumors in ratswere diagnosed as mixed pattern hepatocarcinoma. (3) Bone marrow mesenchymalstem cells were separated, and we found there were 85.4% MSCs in all cells.二(1)The inhibition ratio of E-ADM (E-Adriamycin),and 5-FU(5-Fliorouracil),GEM(Gemcitabine),Cyclophosphamide,DDP(Cisplatin) to MSCs were23.32±4.32,27.81±5.02,23.61±3.21,22.14±3.17 and 26.56±4.33; which were different from that of the hepatocarcinoma cells, which were t=7.885, P＜0.001; t=9.363,P＜0.001; t=8.814, P＜0.001; t=12.585, P＜0.001 and t=13.837, P＜0.001.(2)Nocorrelation was found between the inhibition ratio of 5 anticancer drugs onhepatocarcinoma cells and the tumor weight of nudemiceThecorrelationcoefficientwere:r=0.541,(E-ADM,P=0.106);r=0.300,(5-FU,P=0.400);r=-0.356,(GEM,P=0.313);r=0.210,(Cyclophosphamide,P=0.561);andr=0.050,(DDP,P=0.891). But a significant negative correlation was found between theinhibition ratio of 5anticancer drugs on MSCs and the tumor weight of nudemice. Thecorrelationcoefficientwere:r=-0.885,(E-ADM,P=0.001);r=-0.785,(5-FU,P=0.001);r=-0.675,(GEM,P=0.032)r=-0.763,(Cyclophosphamide,P=0.010)andr=-0.695, (DDP,P=0.026).Conclusion: (1) We used 5 different mechanism of action chemotherapeuticswhich were commonly used in clinic. The result shows the hepatocarcinoma cellsfrom the same rat have different drug sensitivity. And the MSCs have different drugsensitivity too. The most effective drug is 5-Fliorouracil, and Gemcitabine＞Cisplatin＞E-Adriamycin＞Cyclophosphamide. The result shows that thestem-like-cells have different drug reaction from ordinary hepatocarcinoma cells.(2)The inhibition ratio of anticancer drugs to MSCs were lower than that it tohepatocarcinoma cells. It suggested that the MSCs had a distinct chemoresistancemechanism like the tumor stem cells.(3) the inhibition ratio of anticancer drugs onhepatocarcinoma cells could not correctly appraise the invasion potential ofhepatocarcinoma cells. However the inhibition ratio of anticancer drugs on MSCscan correctly appraise the invasion potential of hepatocarcinoma cells. So it isfeasible to use the MSCs take place of the TSCs to search for anticancer drugsensitivity.
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