Dual-blocking of PI3K and mTOR improves chemotherapeutic effects on SW620 human colorectal cancer stem cells by inducing differentiation

Min Jung Kim, Jeong Eun Koo, Gi Yeon Han, Buyun Kim, Yoo Sun Lee, Chiyoung Ahn, Chan Wha Kim

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Cancer stem cells (CSCs) have tumor initiation, self-renewal, metastasis and chemoresistance properties in various tumors including colorectal cancer. Targeting of CSCs may be essential to prevent relapse of tumors after chemotherapy. Phosphatidylinositol-3- kinase (PI3K) and mammalian target of rapamycin (mTOR) signals are central regulators of cell growth, proliferation, differentiation, and apoptosis. These pathways are related to colorectal tumorigenesis. This study focused on PI3K and mTOR pathways by inhibition which initiate differentiation of SW620 derived CSCs and investigated its effect on tumor progression. By using rapamycin, LY294002, and NVP-BEZ235, respectively, PI3K and mTOR signals were blocked independently or dually in colorectal CSCs. Colorectal CSCs gained their differentiation property and lost their stemness properties most significantly in dual-blocked CSCs. After treated with anti-cancer drug (paclitaxel) on the differentiated CSCs cell viability, self-renewal ability and differentiation status were analyzed. As a result dual-blocking group has most enhanced sensitivity for anti-cancer drug. Xenograft tumorigenesis assay by using immunodeficiency mice also shows that dual-inhibited group more effectively increased drug sensitivity and suppressed tumor growth compared to single-inhibited groups. Therefore it could have potent anti-cancer effects that dualblocking of PI3K and mTOR induces differentiation and improves chemotherapeutic effects on SW620 human colorectal CSCs.

Original languageEnglish
Pages (from-to)360-370
Number of pages11
JournalJournal of Korean medical science
Volume31
Issue number3
DOIs
Publication statusPublished - 2016

Keywords

  • Cancer stem cells
  • Differentiation therapy
  • Drug resistance
  • MTOR
  • PI3K

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Dual-blocking of PI3K and mTOR improves chemotherapeutic effects on SW620 human colorectal cancer stem cells by inducing differentiation'. Together they form a unique fingerprint.

  • Cite this