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Reversal effects of tetramethylpyrazine on multidrug resistance in hepatocellular carcinoma cells BEL‐7402/ADM by inhibiting calcium pathway (655.6)
Author(s) -
Wang Xuanbin,
Liu Ying,
Li Hongliang,
Liu Ming,
Ouyang Lu,
Wang Linhai,
Xie Yong
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.655.6
Subject(s) - tetramethylpyrazine , hepatocellular carcinoma , chemistry , calcium in biology , pharmacology , reactive oxygen species , multiple drug resistance , ic50 , mapk/erk pathway , calcium , p38 mitogen activated protein kinases , doxorubicin , calcium channel blocker , intracellular , in vitro , kinase , medicine , cancer research , biochemistry , pathology , chemotherapy , alternative medicine , antibiotics , organic chemistry
P‐glycoprotein (P‐gp) was one of mechanisms of Multidrug resistant (MDR) hepatocellular carcinoma (HCC) . Its activation, at least partially depends on protein kinase Cα (PKCα). Tetramethylpyrazine (TMP) is a bioactive constituent isolated from the root of Ligusticum chuanxiong Hort , a Chinese herb. The present study was to investigate if TMP reverses Human drug resistant hepatocellular carcinoma cells BEL‐7402/ADM by inhibiting calcium pathway. We found that t he microscopy showed that the average immunofluorescent intensity of the PKCα level in Bel‐7402/ADM cells treated with TMP was (33.33 ± 1.7) % compared to that of without TMP ( P <0.001). The fluorescent intensity of intracellular Ca 2+ for BEL‐7402/ADM treated with TMP was 541.67±8.15 versus that of without TMP (665.16±2.89) ( P <0.05); CCK‐8 assay showed that when TMP combined with UO126 (ERK blocker) or SP600125(JNK blocker), the IC50 value of doxorubicin on Bel‐7402/ADM was increased. However, when TMP combined with SB203580 (p38 blocker) was treated in Bel‐7402/ADM, the IC50 value was reduced. Furthermore, compared with the control group, the level of intracellular reactive oxygen species (ROS) of TMP group was increased. These suggested that TMP might reversal MDR HCC by downregulating calcium pathway which may be associated with ROS level and MAPK pathway.Grant Funding Source : Supported by Department of Health of Hubei Province, NO. JX5A10;