Realgar transforming solution is involved of JNK, P38 MAPK pathway in down-regulating Ras/MAPK pathway in Caenorhabditis elegans

OBJECTIVE To investigate the effect and the mechanisms of realgar transforming solution（RTS） on down-regulating over activated ras. METHODS we used the optimizing technical processes to obtain the RTS, and evaluate the mechanisms of RTS on down-regulating overactivated ras in Caenorhabditis elegans. RESULTS We found that the mRNA level of let60 and lin45 significantly decreased following exposure to RTS, but mRNA levels of mpk1 were not statistically significant in let60/ras（gf） mutant. RTS together with sorafenib（RAF inhibitors） significantly enhanced the activity of RTS on down-regulating overactivated ras more than RTS only, but 50 μmol·L;PD98059, a specific ERK inhibitor did not. Lin45 gene RNAi decreased the ability of RTS on down-regulating overactivated ras significantly, but mpk1 gene RNAi did not, indicating that the activity of RTS on down-regulating overactivated ras mainly through targeting to lin45/raf. In addition, RTS significantly increased mR NA level of pmk1/p38 and jnk1/jnk in let-60/ras（gf） mutant, 50 μmol·L;SB203580（p38 inhibitor） and SP600125（JNK inhibitor） significantly attenuated the effects of RTS on down-regulating overactivated ras in some degree, and pmk1, jnk1 gene RNAi displayed the similar results, suggesting that P38 and JNK/MAPK pathways in some degree were involved in the effects of RTS on down-regulating overactivated ras in C. elegans. CONCLUSION Realgar transforming solution down-regulate the Ras/MAPK pathway through JNK and P38 MAPK pathways.