论文部分内容阅读
Tumor-targeted drug delivery systems (Tt-DDSs) are proposed as a promising strategy for cancer care.However,the dense collagen network in tumors stroma significantly reduces the penetration and efficacy of Tt-DDS.In order to investigate the effect of asiatic acid (AA) on antitumor effect of pegylated liposomal doxorubicin (PLD) by attenuating stroma-collagen,colon cancer xenograft mice (SW620 cell line) were treated by PLD,AA,or combined regimes,respectively;the collagen levels were estimated by Sirius red/fast green dual staining and immunohistochemistry (IHC) staining;the intratumor exposure of doxorubicin was visualized by ex vivo fluorescence imaging and quantified by HPLC/MS analysis.In addition,the impact of AA on collagen synthesis of fibroblast cell (HFL-1) and cytotoxic effect of PLD and doxorubicin to cancer cell (SW620) were studied in vitro.In the presence of AA (4 mg/kg),the intratumor collagen level was restricted in vivo (reduced by 22%,from 4.14% ± 0.30% to 3.24% ± 0.25%,P =0.051) and in vitro.Subsequently,doxorubicin level was increased by ~30%.The antitumor activity of PLD was significantly improved (57.3% inhibition of tumor growth and 44% reduction in tumor weight) by AA combination.Additionally,no significant improvement in cytotoxic effect of PLD or doxorubicin induced by AA was observed.In conclusion,AA is a promising sensitizer for tumor treatment by enhancing intratumor drug exposure via stromal remodeling.