Dai Lina,Zhang Ping,Su Qin,Wang Jinhua.Ginkgolic acid enhances chemosensitivity of Tca8113 cells via suppressing PKD-2 activity[J].J Amry Med Univ (J Third Mil Med Univ),2012,34(08):729-733.
Dai Lina,Zhang Ping,Su Qin,Wang Jinhua.Ginkgolic acid enhances chemosensitivity of Tca8113 cells via suppressing PKD-2 activity[J].J Amry Med Univ (J Third Mil Med Univ),2012,34(08):729-733.DOI:
Ginkgolic acid enhances chemosensitivity of Tca8113 cells via suppressing PKD-2 activity
Objective To investigate the role of protein kinase D-2 (PKD-2) in chemosensitivity enhanced by ginkgolic acid (GA) in Tca8113 cells. Methods The effect of different concentrations of GA on the proliferation of Tca8113 cells and the cell survival rate for single use of Carboplatin (CBP) or Paclitaxel (PTX) and combination of CBP or P
TX with GA was detected by Methyl thiazolyl tetrazolium( MTT) assay. Western blot analysis was used to detect protein expression of phospho-protein kinase D (p-PKD-2) and PKD-2 in Tca8113 cells induced by GA for different times. shRNA was introduced to downregulate the expression of PKD-2 in Tca8113 cells. Phorbol 12-myristate 13-acetate (PMA) was used to induce the phosphorylation of PKD-2. MTT assay was used to detect viability after exposure of cells to drugs or combination of drugs and GA. Results The IC
50
of GA which was detected by MTT was 20 mg/L.The folds of chemosensitivity of Tca8113 to CBP and PTX enhanced by GA were 4.37 and 39.20 respectively. Exposure of Tca8113 cells to GA resulted in a decrease in phospho-PKD-2 level in a time-dependent manner. Knockdown of PKD-2 with shRNA enhanced chemosensitivity of Tca8113 cells to CBP and PTX or combination with GA
with the folds of 1.651 7 and 1.501 6 respectively. GA also antagonized the function of PMA
which induced the phosphorylated activation of PKD2 and increased chemotherapy drugs resistance of Tca8113 cells. Conclusion GA may promote chemosensitivity of Tca8113 cells via inhibiting phosphorylation of PKD-2 pathway.