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Down‐regulation of BMI‐1 cooperates with artemisinin on growth inhibition of nasopharyngeal carcinoma cells
Author(s) -
Wu Jing,
Hu Dong,
Yang Guang,
Zhou Junyi,
Yang Changfu,
Gao Yun,
Zhu Zhenyu
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23114
Subject(s) - artemisinin , nasopharyngeal carcinoma , cancer research , cell culture , gene knockdown , cell cycle checkpoint , chemosensitizer , cell growth , cell cycle , growth inhibition , pharmacology , biology , cancer , medicine , immunology , drug resistance , malaria , plasmodium falciparum , radiation therapy , multiple drug resistance , microbiology and biotechnology , biochemistry , genetics
Artemisinin and its derivatives are well known antimalaria drugs, particularly useful for the treatment of infection of Plasmodium falciparum malaria parasites resistant to traditional antimalarial pharmaceuticals. Artemisinin has inhibitory effects on cancer cell growth and anti‐angiogenetic activity, including many drug‐ and radiation‐resistant cancer cell lines. Moloney murine leukemia virus insertion site 1 (BMI‐1) has been shown to regulate proliferation by inhibiting p16 ink4a transcription. It is well known that BMI‐1 over‐expression was found in nasopharyngeal carcinoma cell lines and correlated with advanced invasive stage of the tumor progression and poor prognosis. In the present investigation, we analyzed the inhibitory effects of artemisinin on proliferation of nasopharyngeal carcinoma cell lines (CNE‐1 and CNE‐2, well‐differentiated cells, and poorly differentiated cells). We demonstrated that artemisinin induced G1 cell cycle arrest in CNE‐1 and CNE‐2 cells. Artemisinin inhibited BMI‐1 both in protein and transcript levels. BMI‐1 knockdown made the cells more sensitive to artemisinin with an increase in G1 phase, but over‐expression of BMI‐1 partially reversed the artemisinin‐induced G1 cell cycle arrest. Depletion of BMI‐1 was able to intensifying the increment of p16 and the reduction of CDK4 induced by artemisinin. In addition, over‐expression of BMI‐1 was capable of attenuating the increasing p16 and decreasing CDK4 in cells treated with artemisinin. Taking together, the BMI1‐p16/CDK4 axis was involved in the artemisinin‐driven G1 arrest in nasopharyngeal carcinoma cells, and these results indicated that a potential treatment that the combination of artemisinin and BMI‐1 downregulation could enhance the growth inhibitory affects on nasopharyngeal carcinoma cells. J. Cell. Biochem. 112: 1938–1948, 2011. © 2011 Wiley‐Liss, Inc.