Mechanism of multidrug resistance of colon cancer cell reversed by Jianpijiedu Herb
LI Xian-qian
WU Jia-xi
FAN Zhong-ze
SUN Yan-ni
GAO Hong
Abstract:Objective To investigate the mechanism of which Chinese traditional medicine , Jianpijiedu ( JBJD) herb protocol reverses multidrug resistance ( MDR) of colon cancer .Methods Sensitivity of Vincristine to colon cancer cells ( HCT-8/V) were detected by cell growth inhibition metods befor or after the treatment of Jianpijiedu Herb .Expression of multidrug gene 1 ( MDR-1) and phosphorylation of Akt in cancer cell were studied by either real -time PCR or Western blot.Results After HCT-8/V was co-cultured with serum containing 20% of JBJD for 24 h, 48 h and 72 h, inhibition rates on proliferation of HCT-8/V resulted by Vincristine were 5.9%, 11.0% and 15.0%, respectively, and all higher than that of the blank control group (all P<0.05).Inhibiting cell growth of Vincristine was positively correlated to the co-culture time and the serum concentration of JBJD .JBJD down-regulated the expression of MDR-1 protein and mRNA in HCT-8/V(P<0.05).Expression of MDR-1 was positively related with the decreased degree of Akt phosphorylation induced by JBJD, and negatively correlated with sensitivity of Vincristine .JBJD combined with PI3K inhibitor(LY294002) resulted in significant deduction of MDR-1 expression at mRNA and protein levels (P-gp) and Akt phosphorylation (p-Akt), and enhanced Vincristine sensitivity significantly than that by single use of JBJD or LY 294002 .Conclusion JBJD effectively turn down activity of PI 3K/Akt signaling pathways by deduction of cellular Akt phosphorylation , which down-regulate the expression of MDR1, increase the sensitivity of Vincristine .
Keywords:colon cancerJianpijiedu herbmultidrug resistancePI3K/Akt signaling
Publication Date:2014-01-01
Online Publishing Date:2025-08-15(First online date of this platform, not the publication date of the document)
Pages:4( 13-16 )
