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

6 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

Fingerprint

Phosphatidylinositol 3-Kinase
Neoplastic Stem Cells
Sirolimus
Cell Differentiation
Colorectal Neoplasms
Neoplasms
Carcinogenesis
Pharmaceutical Preparations
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Growth
Paclitaxel
Heterografts
Cell Survival
Cell Proliferation
Apoptosis
Neoplasm Metastasis
Recurrence
Drug Therapy

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Dual-blocking of PI3K and mTOR improves chemotherapeutic effects on SW620 human colorectal cancer stem cells by inducing differentiation. / Kim, Min Jung; Koo, Jeong Eun; Han, Gi Yeon; Kim, Buyun; Lee, Yoo Sun; Ahn, Chiyoung; Kim, Chan Wha.

In: Journal of Korean Medical Science, Vol. 31, No. 3, 2016, p. 360-370.

Research output: Contribution to journalArticle

Kim, Min Jung ; Koo, Jeong Eun ; Han, Gi Yeon ; Kim, Buyun ; Lee, Yoo Sun ; Ahn, Chiyoung ; Kim, Chan Wha. / Dual-blocking of PI3K and mTOR improves chemotherapeutic effects on SW620 human colorectal cancer stem cells by inducing differentiation. In: Journal of Korean Medical Science. 2016 ; Vol. 31, No. 3. pp. 360-370.
@article{fec5514fbea949fbac78285cc8843cb9,
title = "Dual-blocking of PI3K and mTOR improves chemotherapeutic effects on SW620 human colorectal cancer stem cells by inducing differentiation",
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.",
keywords = "Cancer stem cells, Differentiation therapy, Drug resistance, MTOR, PI3K",
author = "Kim, {Min Jung} and Koo, {Jeong Eun} and Han, {Gi Yeon} and Buyun Kim and Lee, {Yoo Sun} and Chiyoung Ahn and Kim, {Chan Wha}",
year = "2016",
doi = "10.3346/jkms.2016.31.3.360",
language = "English",
volume = "31",
pages = "360--370",
journal = "Journal of Korean Medical Science",
issn = "1011-8934",
publisher = "Korean Academy of Medical Science",
number = "3",

}

TY - JOUR

T1 - Dual-blocking of PI3K and mTOR improves chemotherapeutic effects on SW620 human colorectal cancer stem cells by inducing differentiation

AU - Kim, Min Jung

AU - Koo, Jeong Eun

AU - Han, Gi Yeon

AU - Kim, Buyun

AU - Lee, Yoo Sun

AU - Ahn, Chiyoung

AU - Kim, Chan Wha

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Cancer stem cells

KW - Differentiation therapy

KW - Drug resistance

KW - MTOR

KW - PI3K

UR - http://www.scopus.com/inward/record.url?scp=84960415202&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84960415202&partnerID=8YFLogxK

U2 - 10.3346/jkms.2016.31.3.360

DO - 10.3346/jkms.2016.31.3.360

M3 - Article

C2 - 26955235

AN - SCOPUS:84960415202

VL - 31

SP - 360

EP - 370

JO - Journal of Korean Medical Science

JF - Journal of Korean Medical Science

SN - 1011-8934

IS - 3

ER -