Antitumor activity of folate-targeted, paclitaxel-loaded polymeric micelles on a human esophageal EC9706 cancer cell line

Abstract

Wenbin Wu,1 Yonghui Zheng,2 Rui Wang,2 Weili Huang,3 Lei Liu,2 Xiuli Hu,2 Shi Liu,2 Jun Yue,2 Ti Tong,1 Xiabin Jing21Department of Thoracic Surgery, Second Hospital of Jilin University, Changchun, 2State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 3Department of Gastroenterology, the Affiliated Hospital of Beihua University, Jilin, ChinaBackground: Esophageal cancer is recognized as one of the most refractory pernicious diseases. In addition, it is an aggressive malignancy with a propensity for local progression and distant dissemination. Because of the poor long-term prognosis for patients with esophageal cancer, increasing attention has focused on the integration of targeted agents into current therapeutics. Nevertheless, there have been few studies reported concerning the therapeutic efficacy of paclitaxel-conjugated polymeric micelles in human esophageal cancer in vivo. Therefore, the aim of this research was to investigate the tumor inhibition effect of composite micelles containing folic acid and paclitaxel on the human esophageal EC9706 cancer cell line.Methods and results: Intravenous administration of folate-targeted, paclitaxel-loaded micelles was demonstrated to be more efficient in inhibiting subcutaneous xenograft tumors and extending the survival rate of tumor-bearing nude mice than free paclitaxel and plain paclitaxel micelles at an equivalent paclitaxel dose of 20 mg/kg, which was further backed up by flow cytometry, TUNEL, and expression of apoptosis-related proteins, including Bax, Bcl2, and caspase 3 in this study.Conclusion: The folate-mediated paclitaxel-loaded polymeric micelle is a promising agent for the treatment of human esophageal cancer.Keywords: esophageal cancer, folate, paclitaxel, polymer-drug conjugate, targeted drug delivery