The synergistic efficacy and preliminary safety exploration of ligustilide and temozolomide against glioma in vitro and in vivo
Objective:To investigate the synergistic anti-glioma effects of ligustilide(LIG)co-administered with temozolomide(TMZ)both in vivo and in vitro and to preliminarily study the safety of the combination.Methods:CCK-8 method was used to detect the effects of TMZ and LIG alone or in combination on the proliferation of U251 cells.The synergistic antitumor effect of the combination of the two drugs in vitro was assessed by the Q-value of the Jin Jung Mean method.A C6 graft glioma rat model was established to investigate the effects of TMZ and LIG alone and in combination via tail vein administration on the growth of subcutaneous graft tumors in rats.The tumor suppression rate was calculated and the synergistic anti-tumor effects in vivo was evaluated in combination with HE staining results.Preliminary safety evaluation of the combination was carried out using organ coefficients and HE staining pathologic observations of each tissue and organ.Results:LIG and TMZ had a synergistic inhibitory effect on U251 cell viability at ratios ranging 8∶1～8∶5.The Q value was highest and the synergistic effect was strongest when the coadministration ratio was 4∶1.The results of in vivo experiments showed that the combination of 18.47 mg·kg-1 TMZ and 4.61 mg·kg-1 LIG injected intravenously via the tail vein had a significant inhibitory effect on the tumor growth in the rat transplantation tumor model(P＜0.05,0.01).Tissue sections of transplanted tumors showed that the necrosis of tumor tissues was the severest in this dose combination group.There was no significant difference in organ coefficients of each dosing group compared with the control group,and HE pathological tissue observation of each tissue and organ did not elucidate stronger tissue abnormality.Conclusion:Co-administration of TMZ and LIG at a mass ratio of 4∶1 preliminarily showed synergistic anti-glioma effects both in vivo and in vitro as well as unobvious organ damage.
ligustilidetemozolomidegliomaproliferationcombination drug deliveryanti-tumor
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