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Asiatic acid enhances intratumor delivery and the antitumor effect of pegylated liposomal doxorubicin by reducing tumor-stroma collagen

  
@article{APS9952,
	author = {Luo Fang and Si-si Kong and Li-ke Zhong and Can-ming Wang and Yu-jia Liu and Hai-ying Ding and Jiao Sun and Yi-wen Zhang and Fan-zhu Li and Ping Huang},
	title = {Asiatic acid enhances intratumor delivery and the antitumor effect of pegylated liposomal doxorubicin by reducing tumor-stroma collagen},
	journal = {Acta Pharmacologica Sinica},
	volume = {40},
	number = {4},
	year = {2019},
	keywords = {},
	abstract = {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.},
	url = {http://www.chinaphar.com/article/view/9952}
}