Targeting Lung Cancer Stem Cells Using Combination of Tel and Docetaxel Liposomes in 3D Cultures and Tumor Xenografts

Overview

Journal Toxicol Appl Pharmacol

Specialties Pharmacology
Toxicology

Date 2020 Jun 17

PMID 32540278

Citations 13

Authors

Peggy Arthur

Nilkumar Patel

Sunil Kumar Surapaneni

Arindam Mondal

Aragaw Gebeyehu

Arvind Bagde

Shallu Kutlehria

Ebony Nottingham

Mandip Singh

Affiliations

Soon will be listed here.

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.

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