Tumor targeting with docosahexaenoic acid-conjugated docetaxel for inhibiting lung cancer metastasis to bone.

Abstract

Docetaxel (DTX) is currently used as a first- or second-line drug treatment for patients with lung cancer, however, it is less effective for the treatment of patients with bone metastasis of lung cancer. This is primarily due to the fact that docetaxel is nonspecific. In the present study, docosahexaenoic acid (DHA) was selected as a tumor-targeting ligand, and DHA-conjugated DTX (DTX-DHA) was prepared for inhibiting lung cancer metastasis to bone. The anti-cancer activity assay revealed that DTX-DHA exhibited a similar antitumor efficacy to DTX in vitro. The maximum tolerated dose of DTX-DHA was increased compared with that of DTX. The present study results indicated that DTX-DHA exhibited an improved inhibition efficacy of lung cancer metastasis to bone in comparison with DTX in vivo. Encouragingly, the mean survival time of the DTX-DHA group (30.60 days) was increased compared with the DTX group (26.10 days; P<0.01). Furthermore, the results of cell migration and osteoclast-induced formation assays suggested that DTX-DHA inhibited lung cancer metastasis to bone primarily by affecting lung cancer cell migration. These results indicate that DTX-DHA may exhibit a potential therapeutic effect against lung cancer metastasis to bone.