Regorafenib suppresses colon tumorigenesis and the generation of drug resistant cancer stem-like cells via modulation of miR-34a associated signaling

Journal of Experimental & Clinical Cancer Research : CR
Mao-Hua CaiYue-Xing Tu

Abstract

Colorectal cancer (CRC) is one of the most prevalent malignancies in the world and developed drug resistance has represented one of the most challenging tasks for management. The current therapeutic regimens may select and enrich cancer stem-like cells (CSCs) resulting in the increased resistance against treatment, metastatic potential and mortality. Regorafenib is a multi-kinase inhibitor, an FDA-approved last-of-line treatment for patients with chemo-refractory metastatic CRC. However, regorafenib's potential effects on CSCs have not been fully elucidated. Here, we developed two 5-FU resistant CRC cell lines, HCT-116R and DLD-1R and showed the increased CSCs characteristics such as increased side-population cells, tumor sphere formation and expression of stemness markers. These cell lines and CSCs properties were used for evaluating the potential of regorafenib in suppressing CSCs. We showed that regorafenib treatment decreased the stemness phenotypes including tumor sphere formation, and side-population, of both HCT-116R and DLD-1R cells. Additionally, regorafenib suppressed the cell viability in both cell lines synergistically with 5-FU. In vivo, the combination of regorafenib and 5-FU significantly suppressed the tumorigen...Continue Reading

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Citations

Nov 13, 2018·Journal of Cellular Physiology·Masoud NajafiKeywan Mortezaee
Dec 19, 2018·Journal of Experimental & Clinical Cancer Research : CR·Maria Elena PisanuRita Mancini
Mar 13, 2020·International Journal of Cancer. Journal International Du Cancer·Sarun JuengpanichXiujun Cai
Jun 27, 2020·Cancer Biology & Therapy·Chunhua ZhouLulu Zhai
Sep 20, 2018·International Journal of Molecular Sciences·Lei DingQinghua Cui
Feb 12, 2021·Pharmaceuticals·Eunsun JungTae-Su Han
Feb 11, 2021·International Journal of Molecular Sciences·Andrea AngiusMaria Rosaria De Miglio
Feb 17, 2021·Signal Transduction and Targeted Therapy·He-Ming ZhouQin Li
Mar 20, 2021·Seminars in Cancer Biology·Rui ZhangSuling Liu

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Methods Mentioned

BETA
PCR
xenograft

Clinical Trials Mentioned

NCT03099486

Software Mentioned

TargetScan

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