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Dual-Blocking of PI3K and mTOR Improves Chemotherapeutic Effects on SW620 Human
Colorectal Cancer Stem Cells by Inducing Differentiation
#MMPMID26955235
Kim MJ
; Koo JE
; Han GY
; Kim B
; Lee YS
; Ahn C
; Kim CW
J Korean Med Sci
2016[Mar]; 31
(3
): 360-70
PMID26955235
show ga
Cancer stem cells (CSCs) have tumor initiation, self-renewal, metastasis and
chemo-resistance 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 dual-blocking of PI3K and mTOR induces differentiation and improves
chemotherapeutic effects on SW620 human colorectal CSCs.
|*Phosphoinositide-3 Kinase Inhibitors
[MESH]
|AC133 Antigen/genetics/metabolism
[MESH]
|Animals
[MESH]
|Antineoplastic Agents/pharmacology/therapeutic use
[MESH]
free
free
free
