Literature DB >> 32540278

Targeting lung cancer stem cells using combination of Tel and Docetaxel liposomes in 3D cultures and tumor xenografts.

Peggy Arthur1, Nilkumar Patel1, Sunil Kumar Surapaneni1, Arindam Mondal2, Aragaw Gebeyehu1, Arvind Bagde1, Shallu Kutlehria1, Ebony Nottingham1, Mandip Singh3.   

Abstract

Cancer stem cells (CSCs) accounts for recurrence and resistance to chemotherapy in various tumors. Efficacy of chemotherapeutic drugs is limited by tumor stromal barriers, which hinder their penetration into deep tumor sites. We have earlier shown telmisartan (Tel) pretreatment prior to Docetaxel (DTX) administration enhances anti-cancer effects in non-small cell lung cancer (NSCLC). Herein, we demonstrated for the first time the efficacy of Docetaxel liposomes (DTXPL) in combination with Tel in 3D cultures of H460 cells by using polysaccharide-based hydrogels (TheWell Biosciences) and also in xenograft model of DTX resistant H460 derived CD133+ lung tumors. DTXPL and Tel combination showed enhanced cytotoxicity in H460 WT 3D cultures by two folds. In H460 3D cultures, Tel pretreatment showed increased liposomal uptake. DTXPL and Tel combination treated tumors showed reduction in tumor volume (p < .001), increased apoptosis and downregulation of CSC markers (p < .01) in H460 WT and DTX resistant CD133+ xenograft models.
Copyright © 2020 Elsevier Inc. All rights reserved.

Entities:  

Keywords:  Cancer Stem Cells (CSC); Docetaxel (DTX); Docetaxel Loaded PEGylated Liposomes (DTXPL); Non-small Cell Lung Cancer (NSCLC); Resistance; Telmisartan (Tel)

Mesh：

Substances：

Year:  2020        PMID： 32540278      PMCID： PMC7437978          DOI： 10.1016/j.taap.2020.115112

Source DB:  PubMed          Journal:  Toxicol Appl Pharmacol        ISSN： 0041-008X            Impact factor:   4.219


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