Tanshinone II A improves distribution and anti-tumor efficacy of pegylated liposomal doxorubicin via normalizing the structure and function of tumor vasculature in hepa1-6 hepatoma mice model

OBJECTIVE

To investigate whether the Tan II A could improve the distribution and anti-tumor efficacy of Pegylated Liposomal Doxorubicin (PLD) via normalizing the structure and function of vasculature in Hepa1-6 hepatoma mice model.

METHODS

Hepa1-6 hepatoma-bearing mice were treated with Tan II A for 14 d. Distribution and anti-tumor efficacy of PLD, and the structure and function of the tumor vasculature were evaluated using various techniques.

RESULTS

Tan II A significantly reduced the micro-vessel density (MVD). After Tan II A treatment, the tumor vascular walls were better structured, as the increased coverage of the pericytes and the promoted contact of the basement membrane and endothelial cell. Functional tests showed that tumor hypoxia was improved and the exudation amount of Evans blue in the parenchyma of the tumor decreased. In addition, mice treated with Tan II A had greater PLD penetration distance intratumorally. Furthermore, combined therapy of Tan II A and PLD significantly inhibited tumor growth.

CONCLUSION

This study suggests that Tan II A helps normalizing the tumor vasculature and has therapeutic potential in increasing the distribution of chemotherapy drug in the tumor.