Tumor metastasis would seriously impair the efficacy of
chemotherapy. Our previous studies showed
losartan combined with
paclitaxel-loaded pH-sensitive cleavable
liposomes (PTX-Cl-Lip) facilitated
paclitaxel accumulation and led to enhanced antitumor efficacy in 4T1 bearing mice. Since
losartan could inhibit the level of
collagen I which was related to
tumor metastasis, this strategy was further applied to suppress
tumor metastasis this time. Our in vivo anti-metastatic study manifested
losartan could lower the colonies occupied in lungs by 76.4% compared with that of saline group. When
losartan and PTX-Cl-Lip were combined, anti-metastatic efficiency reached to 88.2%, which was the best among all the groups. In vitro 3D
tumor spheroids studies proved
losartan could significantly suppress the invasion of
tumor cells.
Losartan plus PTX-Cl-Lip could further weaken the
metastasis of
tumor cells. Mechanism study showed the declination of
collagen I level via
losartan was caused by inhibition of active transforming growth factor-β1. Western-blot study showed
losartan could decrease the level of
lysyl oxidase, then inhibit the cross-linking of
collagen I, finally weakened the cell signaling transmit via
integrin and the
metastasis of
tumor cells was restrained. All above studies illustrated this combined tactic could achieve favorable effect on suppression of lung
tumor metastasis.