| There are numerous plants in the nature, among which many might be used as chemopreventive agents. Could we separate the effective components of them, study on their chemical and biological properties, it would be very helpful to the development of novel anti-cancer drugs. In this study, we used cultured cancer cell lines as the experiment model, evaluated the growth inhibitory effects of extracts of the Chinese herbs towards cancer cells in vitro. The methods of MTT assay and soft agar colony formation assay were employed. We screened out several extracts that had the characteristic of inhibiting the growth or proliferation of cancer cells at very low concentration (microgramme/ml level). Among the screened 25 extracts, about 12 might have the potential of tumor suppression. We could see under the microscope cells treated with such drugs usually exhibited similar morphological changes including cell shrinkage, nuclear condensation, and so on. Some of the effective extracts have high purity and their inhibitory concentrations towards cancer cells could be as low as the level of microgramme per microlitre, which may approach theirlevelsin plasma or tissues. Then we used BALB/C mice as the experiment model, to detected the in vivo anticancer activity of curcumin and silymarin. Animal experiment demonstrated that neither curcumin nor silymarin has acute toxicity, and the effect of silymarin accorded with the standard of in vivo tumor inhibitory assay. Compared to the untreated group and olive oil treated group, the mean weight of tumor tissues of curcumin 'treated group were much less, but the difference between them was not significant and the weight of tumor tissues varied between a wide range.According to the results of the first part, we chose two purified agents, curcumin and silymarin, to the further study on their inhibitory mechanisms. Curcumin had a very strong inhibitory effect on almost all of cancer cell lines examined. So we treated the multidrug resistant human gastric adenocarcinoma cell line SGC7901/VCR with curcumin, observed the changes of cells, and evaluated the inhibitory effects and the cooperational effects with conventional chemopreventive drugs, such as adriamycin (ADR), 5-fluorouracil (5-FU) and vincristine (VCR). Then we examined the death mode of treated cells and further studied the related molecular mechanisms. Firstly, it was confirmed that the MDR human gastric adenocarcinoma cell line SGC7901/VCR was sensitive to curcumin by MTT assay. Secondly, we found curcumin of subdosage had the cooperational effects with conventional chemopreventive drugs, including with the peak plasma concentration of ADR, with 0.1,1 or 10 times of the peak plasma concentration of 5-FU, and with the peak plasma concentration of VCR. In another word, curcumin might reverse the multidrug resistance of SGC7901/VCR, To find out the mode of cell death after curcumin treatment, we detected DNA ladder by agarose gel electrophoresis, and PARP cleavage by Western blot. The results demonstrated that curcmin induced apoptosis in SGC7901/VCR cells in a time-and dose-dependent manner. Previous study showed that mitogen activated protein kinase (MAPK) family members were involved in the progress of multidrug resistance induced by certain chemopreventive agents, such as adriamycin and vincristine. To understand the function of curcumin on MDR cancer cells, and the role of MAPKs in the development of MDR, we explored the alteration of expression and activities of three main MAPK family members, JNK/SAPK, ERK, and p38 mainly by western blotting using antibodies directed against non-phosphorylated and phosphorylated forms of these kinases. After the treatment of various concentration of curcumin for 24hr, the expression level of the three kinases did not changed apparently, while the extent of phosphorylation, which was regarded as a marker for kinase activity, changed significantly. And the extents of phosphorylation of the three kinases were modulated differently. In the three kinases, JNK and ERK displ...
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