Suppression of human breast tumors in NOD/SCID mice by CD44 shRNA gene therapy combined with doxorubicin treatment.
BACKGROUND
Breast cancer stem cells with a CD44(+)CD24(-) phenotype are the origin of breast tumors. Strong CD44 expression in this population indicates its important role in maintaining the stem cell phenotype. Previous studies show that CD44 down-regulation causes CD44(+)CD24(-) breast cancer stem cells to differentiate into non-stem cells that are sensitive to antitumor drugs and lose many characteristics of the original cells. In this study, we determined tumor suppression in non-obese severe combined immunodeficiency mice using CD44 shRNA therapy combined with doxorubicin treatment.


METHODS
Tumor-bearing non-obese severe combined immunodeficiency mice were established by injection of CD44(+)CD24(-) cells. To track CD44(+)CD24(-) cells, green fluorescence protein was stably transduced using a lentiviral vector prior to injection into mice. The amount of CD44 shRNA lentiviral vector used for transduction was based on CD44 down-regulation by in vitro CD44 shRNA transduction. Mice were treated with direct injection of CD44 shRNA lentiviral vector into tumors followed by doxorubicin administration after 48 hours. The effect was evaluated by changes in the size and weight of tumors compared with that of the control.


RESULTS
The combination of CD44 down-regulation and doxorubicin strongly suppressed tumor growth with significant differences in tumor sizes and weights compared with that of CD44 down-regulation or doxorubicin treatment alone. In the combination of CD44 down-regulation and doxorubicin group, the tumor weight was significantly decreased by 4.38-fold compared with that of the control group.


CONCLUSIONS
These results support a new strategy for breast cancer treatment by combining gene therapy with chemotherapy.
Laboratory of Stem Cell Research and Application, University of Science, Vietnam National University, HCM City.
Phuc
P
Van Pham
Ngoc Bich
NB
Vu
Thuy Thanh
TT
Duong
Tam Thanh
TT
Nguyen
Nhung Hai
NH
Truong
Nhan Lu Chinh
NL
Phan
Tue Gia
TG
Vuong
Viet Quoc
VQ
Pham
Hoang Minh
HM
Nguyen
Kha The
KT
Nguyen
Nhung Thi
NT
Nguyen
Khue Gia
KG
Nguyen
Lam Tan
LT
Khat
Dong
D
Van Le
Kiet Dinh
KD
Truong
Ngoc Kim
NK
Phan