JAK2 and MAPK pathways are involved in the inhibitory effect of berberine hydrochloride on gastric cancer cell proliferation and IL-8 secretion

摘要

Acknowledgements This work was supported by Educational Commission of Shanghai of China （2012JW19）; Key Research Innovation Project （13ZZ099）; Key Project from Department of Education of China （20123107130002）; Shanghai Eastern Scholar Program （2013-59） and Shanghai E-research Institute of Bioactive Constituent in TCM plan. Abstract： Aim This investigation was to identify whether Janus-activated kinase 2 （JAK2） and mitogen-activated protein kinase （MAPK） pathways were involved in the inhibitory effect of berberine hydrochloride （BER） on gastric cancer cell proliferation and IL-8 expression in vitro and in vivo. Methods CCK- 8 assay was used to assess the cell proliferation. IL-8 production was determined by ELISA and qPCR assay. Mo- lecular pathways involved were evaluated by ELISA and western-blotting methods. Results BER time- and dose- dependently inhibited the proliferation of MGC 803 and AGS cells. It also suppressed tumor growth in nude mice xenografted with MGC 803 cells. In addition, BER reduced interleukin-8 （IL-8） secretion of AGS cells as well as MGC 803 cells both in vitro and in vivo. Further study disclosed that inactivation of JAK2, p38 MAPK, ERK1/2 and JNK by BER contributed to the decreased proliferation and tumor growth as well as IL-8 expression in gastric cancer. Although there was no significantly synergistic inhibitory effect between BER and evodiamine on gastric cancer cell proliferation and tumor growth, BER could counteract the up-regulation of IL-8 induced by evodiamine in vitro and vivo. Conclusions Our results suggested that BER might be an efficient and safe drug candidate for treating gastric cancer through JAK2 and MAPK pathways.