Preliminary proteomic analysis of indomethacin's effect on tumor transplanted with colorectal cancer cell in nude mice.
Nonsteroidal anti-inflammatory drugs such as indomethacin (IN) can exert anti-colorectal cancer (CRC) activity through cyclooxygenase independent mechanism, but the exactly biological mechanism is not completely known. Here we use proteomic tools to investigate the molecular mechanism of this action. First, nude mice bearing tumors derived from subcutaneous injection with human CRC cell line HCT116 were randomly allocated to groups treated with or without indomethacin. Later, tumor lumps were incised and then total proteins extracted. After separated with two-dimensional electrophoresis, thirty-one differently expressed spots were found between IN-treated and non-IN-treated groups, of which 25 spots decreased and 6 spots increased in abundance in IN-treated group. Through matrix-assisted laser desorption ionization time of flight mass spectrometry and then NCBInr and SWISS-PROT databases searching, 12 protein spots were finally identified including galectin-1, annexin A1, annexin IV, transcription factor BTF3A, calreticulin. Most of the identified proteins are correlated with tumor's biological properties of proliferation, invasion, apoptosis and immunity, or take part in cell's signal transduction. From above we thought that indomethacin can exert its effect on colorectal cancer through regulating several proteins' expression directly or indirectly. Further study of these proteins may be helpful in founding new targets of drugs for cancer chemotherapy.
Department of Gastroenterology, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, PR China.
Yu-Jie
YJ
Wang
Gui-Ying
GY
Zhang
Zhi-Qiang
ZQ
Xiao
Hong-Mei
HM
Wang
Zhu-Chu
ZC
Chen
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000188:drug therapy*; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D007213:Indomethacin