The Role Of GRP78 In Regulating Natural Factors Of Plant Origin On C6Glioma Cells Cytotoxicity

GRP78 is a chaperone protein which is involve in the signal transduction of many kind of cancers.However,few were known about the regulation style of GRP78 to growth and proliferation of tumor cells so further studies were needed.In this study,we investigated whether the sensitivity of C6 glioma cells to curcumin(CM)was altered by regulated their extracellular glucose level or by a method that transfection GRP78 siRNA to inhibitexpression level of GRP78 in C6 glioma cells.We also choosed the small molecule active components extracted fromDendrobium candidum as a alternative material of CM,and tested their activity in treated tumor cells as above.(1)Data showed that compared to primary cultures of astroglia,CM inhibited glioma cells selectively which was related to intracellular GRP78 level in differente kind of cells.C6 cells were more sensitive to CM when intracellular GRP78 was reduced either by high glucose-medium culture or by transfection of GRP78 si RNA.However,in treated astroglia cells,there was no significant difference in intracellular GRP78 level as well assentivity to CM.(2)Further study indicated that CM also inhibited xenografted C6 glioma cells in zebrafish yolk sac.Intriguingly,at its maximum tolerant concentration(MTC),a dosage that was not toxic to the fish and C6 cells,CM combined with high glucose was more significantly efficient to inhibit C6 glioma xenografts than did CM single.These data suggest that a combination ofGRP78 depletion by high glucose with CM is probably an alternative selection to control glioma.(3)However,the small molecular components extracted from D.candidumhave no activity in proliferation-inhibiting of C6 cells treatedwith high glucose medium.Therefore,small-molecule extract of D.candidum may not play a similar role as CM in proliferation-controlling of C6 glioma cells.