| Leukemia is one of the severe diseases which endanger the health of the human being. The incidence of the disease is about 3-4/100,000 in China. Especially T lymphoblast leukemia, with its acute attack, high malignity, high recurrence, and poor prognosis, badly imperils the lives of children. To induce of PCD of tumor cells is an important strategy in neoplasma therapy. Because of lower side effect and obvious curative effect, some extracts from traditional Chinese herb have been put to the front in new tumor therapeutic drug investigation and development The proliferation inhibition and PCD induction of matrine to acute lymphoblast leukemia JM cell strain make it a promising medicine in leukemia therapy. So, to understand the molecular mechanism in this model is crucial.At the 2nd day JM cells were cultured with matrine, there appeared a lot Of vacuoles in cytoplasm, which were more prominent, showed a time and dosage dependence, then followed by morphological apoptosis characteristics. These features just fall into the criteria of ACD. Naturally, we come to consider the roles of these vacuoles in ACD occurrence. Out of regard for more and more evidence of participation of lysosomal hydrolytic proteases, especially cathepsin D to different PCD models, we suppose to demostrate the expression of cathepsin D on ACD of JM induced by matrine.Our immunohistochemical staining shown that cathepsin D positive signal intensively located in cytoplasm and nucleolus of those cells with apoptotic characterestic in both treatment and control group. While the rate of positive cells to 1000 positive and negative cells in treatment group was significantly higher than that in control. PT-PCR and western blot results shown that after treatment by matrine, the expression of cathepsin D was up-regulated in both transcriptional and translational levels. While the signal of 52kD procathepsin D was stronger in treatment group than that in control, and the pattern of 32kD processed form was just the opposite. Most interestingly, the ACD could be inhibited by cathepsin D inhibitor pepstatin A. That means the up-regulation of cathepsin D is indispensable in matrine induced ACD. Indeed, this alkaloid can interfere the process of procathepsin D (52kD) to its mature form(32kD), and result in the arrest of 52kD form. So, we suppose that theACD maybe was mediated by progenitor form of cathepsin D. Also, Fas-1 is likely involved in this death pathway.To study the expression of cathepsin D in the germinal center of follicular lymphoma and follicular hyperplasia. We conducted Immunohistochemical staining to detect the expression of cathepsin D in paraffin sections of 10 cases of follicular lymphoma and 9 cases of follicular hyperplasia and found that Cathepsin D was expressed intensively in plasmas of dendritic cells scattered in the germinal centers of 9 cases of follicular hyperplasia, while it was moderately expressed in plasmas of dendritic cells dispersed predominantly in the peripheral areas of germinal centers of 10 cases of follicular lymphoma Some germinal centers in 4 cases of follicular lymphoma were surrounded by residual mantle zone cells. At the same time, cathepsin D positive cells in these germinal centers are more than that in germinal centers without mantle zone surrounding in other 6 cases of follicular lymphoma. Tumor cells in germinal centers of follicular lymphoma and B lymphocytes of follicular hyperplasia are negative. That indicates that cathepsin D is a good marker for the dendritic cells and its differential expression in follicular lymphoma and follicular hyperplasia is helpful in the differential diagnosis of the diseases. Based on the former reports of cathepsin D with its important roles in antigen processing, we suppose that lower expression of this protease is probably due to the decreased immunological response ability totumor of follicular lymphoma patients.
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