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Indian Journal of Experimental Biology (IJEB) >
IJEB Vol.49 [2011] >
IJEB Vol.49(02) [February 2011] >
| Title: | Silencing of Bmi-1 gene by RNA interference enhances sensitivity to doxorubicin in breast cancer cells |
| Authors: | Wu, Xiangmei
Liu, Xing
Sengupta, Joyeeta
Bu, Youquan
Yi, Faping
Wang, Changdong
Shi, Yanyan
Zhu, Yong
Jiao, Qingfang
Song, Fangzhou |
| Keywords: | RNA interference
Bmi-1
Breast cancer
Doxorubicin |
| Issue Date: | Feb-2011 |
| Publisher: | NISCAIR-CSIR, India |
| Abstract: | The
oncogene Bmi-1 is highly up-regulated in breast carcinoma and is found to be
efficient in preventing apoptosis of the cancer cells. Doxorubicin is an important
chemotherapeutic agent against breast carcinoma. However, the effective
therapeutic response to doxorubicin is often associated with severe toxicity.
The present study is targetted at developing a strategy to increase doxorubicin
sensitivity to lower doses without compromising its efficacy. A stable cell
line with a persistent silencing of Bmi-1 was established. MTT assay was
performed to evaluate 50% inhibitory concentration (IC50) values of
doxorubicin. Apoptosis was detected by FCM and the expression of related genes [phosphor-Akt
(pAkt), totle-Akt (tAkt), Bcl-2 and Bax] was studied by Western blot. In vivo, the sensitivity of the tumor
tissues against doxorubicin was evaluated by transplanted MCF-7 nude mice model
and the apoptosis of tissue cells was detected by TUNEL assay. The
expression of pAkt and Bcl-2 was
down-regulated, whereas Bax was up-regulated in Bmi-1 silencing cells. The results obtained indicated that silencing of Bmi-1 can render MCF-7
cells more sensitive to doxorubicin which induced a significantly higher
percentage of apoptosis cells in vitro
and in vivo. All together these
results clearly demonstrate that Bmi-1 siliencing combined treatment of
doxorubicin might be a new strategy for biological treatment on breast cancer. |
| Page(s): | 105-112 |
| CC License: |  CC Attribution-Noncommercial-No Derivative Works 2.5 India |
| ISSN: | 0975-1009 (Online); 0019-5189 (Print) |
| Source: | IJEB Vol.49(02) [February 2011]
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