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Dual-Blocking of PI3K and mTOR Improves Chemotherapeutic Effects on SW620 Human Colorectal Cancer Stem Cells by Inducing Differentiation

Authors
Kim, Min-JungKoo, Jeong-EunHan, Gi-YeonKim, BuyunLee, Yoo-SunAhn, ChiyoungKim, Chan-Wha
Issue Date
3월-2016
Publisher
KOREAN ACAD MEDICAL SCIENCES
Keywords
Cancer Stem Cells; PI3K; mTOR; Drug Resistance; Differentiation Therapy
Citation
JOURNAL OF KOREAN MEDICAL SCIENCE, v.31, no.3, pp.360 - +
Indexed
SCIE
SCOPUS
KCI
Journal Title
JOURNAL OF KOREAN MEDICAL SCIENCE
Volume
31
Number
3
Start Page
360
End Page
+
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/89340
DOI
10.3346/jkms.2016.31.3.360
ISSN
1011-8934
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 sternness 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 dual blocking of PI3K and mTOR induces differentiation and improves chemotherapeutic effects on SW620 human colorectal CSCs.
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