β2-adrenoceptor blocker synergizes with gemcitabine to inhibit the proliferation of pancreatic cancer cells via apoptosis induction.

作者: Tao Shan , Qingyong Ma , Dong Zhang , Kun Guo , Han Liu

DOI: 10.1016/J.EJPHAR.2011.04.055

关键词: Internal medicineBcl-2-associated X proteinGemcitabineCancer cellCancerBiologyCancer researchEndocrinologyApoptosisProgrammed cell deathPancreatic cancerPancreatic disease

摘要: The stimulation of β2-adrenoceptor, which is a major mediator for chronic stress-induced cancers, has been implicated in the progression number cancer cells, including pancreatic cancer, remains one most aggressive and lethal diseases worldwide. Whether β-adrenoceptor antagonists potentiate gemcitabine, standard first-line treatment advanced that offers only modest benefit due to acquired chemoresistance, not elucidated. Thus, we studied antiproliferative apoptotic effects underlying mechanisms gemcitabine combined with β2-adrenoceptor blocker ICI 118551 (1-[2,3-(dihydro-7-methyl-1H-iden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol), human BxPC-3 MIA PaCa-2 cells. Results show significantly synergized pro-apoptotic induced by both cells (P<0.05 combination vs. control or alone). When were treated 118551, NF-κB activation was blocked; expression Bax protein substantially increased; Bcl-2 downregulated. Taken together, data suggest potentiates inducing apoptosis Our study implies this may be an effective therapeutic strategy cancer.

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