Arsenic trioxide-mediated growth inhibition in gallbladder carcinoma cells via down-regulation of Cyclin D1 transcription mediated by Sp1 transcription factor.
Gallbladder carcinoma (GBC), an aggressive and mostly lethal malignancy, is known to be resistant to a number of drug stimuli. Here, we demonstrated that arsenic trioxide inhibited the proliferation of gallbladder carcinoma in vivo and in vitro as well as the transcription of cell cycle-related protein Cyclin D1. And, Cyclin D1 overexpression inhibited the negative role of arsenic trioxide in cell cycle progression. We further explored the mechanisms by which arsenic trioxide affected Cyclin D1 transcription and found that the Sp1 transcription factor was down-regulated by arsenic trioxide, with a corresponding decrease in Cyclin D1 promoter activity. Taken together, these results suggested that arsenic trioxide inhibited gallbladder carcinoma cell proliferation via down-regulation of Cyclin D1 transcription in a Sp1-dependent manner, which provided a new mechanism of arsenic trioxide-involved cell proliferation and may have important therapeutic implications in gallbladder carcinoma patients.
Ai
Zhilong
Z
Zhongshan Hospital, Fudan University, Shanghai 200032, People's Republic of China.
Lu
Weiqi
W
Ton
Saixiong
S
Liu
Houbao
H
Sou
Tao
T
Shen
Zhenbin
Z
Qin
Xinyu
X
D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects; D005706:Gallbladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D010087:Oxides / Q000494:pharmacology*; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection
D001152:Arsenicals; D010087:Oxides; D016329:Sp1 Transcription Factor; D019938:Cyclin D1; D000077237:Arsenic Trioxide