Telmisartan Facilitates the Anticancer Effects of CARP-1 Functional Mimetic and Sorafenib in Rociletinib Resistant Non-small Cell Lung Cancer
Sunil Kumar Surapaneni, Ebony Nottingham, Arindam Mondal, Nilkumar Patel, Peggy Arthur, Aragaw Gebeyehu, Anil Kumar Kalvala, Arun K. Rishi, Mandip Singh
Abstract
BACKGROUND/AIM: Tyrosine kinase inhibitors (TKIs) are used for the treatment of both wild type and mutant non-small cell lung cancer (NSCLC); however, acquired resistance is a major clinical challenge. Herein, we aimed to investigate the effects of telmisartan (Tel), CFM 4.16 and sorafenib combination in rociletinib resistant NSCLC tumors. MATERIALS AND METHODS: 3D spheroid cultures and western blotting were used for evaluating cytotoxic effects and protein expression. An in vivo rociletinib resistant H1975 xenograft model of NSCLC was developed by subcutaneous injection of rociletinib resistant H1975 cells into nude mice. RESULTS: Tel, CFM 4.16 and sorafenib combination displayed superior anti-cancer effects in 3D spheroid cultures and a rociletinib resistant H1975 xenograft model of NSCLC by decreasing the protein expression of oncogenic and cancer stem cell markers (Nanog, Sox2 and Oct4). CONCLUSION: Tel facilitates effective penetration of CFM 4.16 and sorafenib in rociletinib resistant H1975 models of NSCLC.