两种第二信使系统在人胃癌MGc80-3细胞增殖分化调节中的相互关系

STUDY ON THE RELATIONSHIP BETWEEN TWO SECOND-MESSENGER PATHWAYS ON THE REGULATION OF PROLIFERATION AND DIFFERENTIATION IN MGc 80-3 CELLS

两种第二信使系统的正负调控作用的假说与细胞增殖失控的癌变机理之间关系,日益引起人们的注意。为此本工作利用HMBA 诱导分化剂和信使通路的阻断剂研究了两种第二信使系统(DG-PKC,cAMP-PKA)在人胃癌MGc80-3细胞生长分化调控过程中的相互关系。人胃癌MGc 80-3细胞在诱导分化剂处理24 h 后,其DG 水平与PKC 活性分别下降了64.7%和28.7%,而cAMP 及其结合蛋白的含量分别上升了62%和32.6%(48 h 后结果更为显著)。PKA-RⅡ表达增强,并从胞质移向核内分布。当用PKC 抑制剂H_7取代HMBA,阻断PKC 通路,24 h 后,DG 水平及PKC 活性均下降,而cAMP 含量上升了1.04倍。反之在HMBA 诱导分化的同时加入PKA 抑制剂使其cAMP 通路受到阻断后,cAMP 及其结合蛋白含量下降。而DG 含量与PKC 活性均上升到与对照组水平相似。PKA-RⅡ又仅仅在胞质中出现。以上实验充分显示了cAMP-PKA 与DG-PKC 两种信使系统在细胞增殖分化中的正负调控作用占有重要地位。

By using an inducer of differentiation(HMBA)and blockers of signal pathways,the relationship between two second-mess-enger pathways(DG-PKC,cAMP-PKA)ininducer-mediated MGc 80-3 cell differentia-tion was studied.Cells were treated with HMBA for24h,levels of DG decreased by 64.7%,activity of PKC decreased by 28.7%,whi-le levels of cAMP and rate of it's proteinbinding increased by 62% and 32.6% re-spectivety(after treated for 48h,the re-sult was more remarkable).PKA-R Ⅱ dist-ributed in nuclei.H_7(PKC inhibitor)was used to sub-stitute for HMBA to block the DG-PKCpathway.After treatment for 24h,the le-vels of DG and activity of PCK both de-creased,while the levels of cAMP increa-sed 1.04 times.On the contrary,PKA inhibitor wasadded while HMBA was used to inducecell differentiation,cAMP-PKA pathwaywas blocked,levels of cAMP and rate ofit's protein binding decreased.But levels ofDG and activity of PKC both increased tothe levels of control cells.At this time,PKA-R Ⅱ distributed only in cytoplasm.These results suggest the harmoniousrelations of the positive and negative re-gulation of cAMP-PKA and DG-PKC sy-stems in cells during the proliferation anddifferentiation of cells.It also showed that positive regulationof PI system may play a leading role inMGc 80-3 cells.It let to normal regulationof two signal pathway out of control toremain maligrant phenotype of these cells.