Effects and mechanism of Ligusticum chuanxiong volatile oil in combination with temozolomide in treatment of glioma by regulating P-gp protein / 中草药

ABSTRACT

Objective: To investigate the anti-tumor effect of Ligusticum chuanxiong volatile oil in combination with temozolomide (TMZ) in the treatment of glioma, and illuminate its possible mechanism. Methods: After C6 glioma animal model was successfully finished, changes of body weight, survival status, tumor volume, and the tumor inhibition rate of rats were detected in the TMZ group and the compatibility group of the volatile oil of L. chuanxiong and TMZ. The concentration of TMZ in the internal and external fluids of U87-MG cells was measured by HPLC after the administration of TMZ and the combination of volatile oil of L. chuanxiong and TMZ, and the differences of the content were analyzed statistically. Western blotting was used to study the effects of TMZ monotherapy, L. chuanxiong volatile oil and TMZ on the expression of P-gp protein of U87-MG cells.Results: Compared with TMZ group, the tumor volume of rats in the compatibility group was significantly decreased (P < 0.05), which was positively correlated with the amount of volatile oil. At the same time, the weight gain of the rats in the compatibility group was increased and the survival status was better. Volatile oil of L. chuanxiong can promote the entry of TMZ into U87-MG cells, and with the increase concentration of volatile oil, the promoting effect was stronger. Volatile oil at 6.25 × 10-3 μL/mL can significantly increase the accumulation of TMZ in the internal fluid (P < 0.05). Western blotting analysis showed that P-gp expressions of cells treated with combination treatment with TMZ (20 μg/mL) and volatile oil [(3.125 × 10-3), (6.25 × 10-3) μL/mL] were markedly down-regulated (P < 0.01), when compared with TMZ group. Conclusion: The volatile oil of L. chuanxiong can promote TMZ entry into glioma cells and then enhance TMZ-induced anticancer efficiency in vivo by inhibiting P-gp expression.