Comparative proteomics of apoptosis initiation induced by 5-fluorouracil in human gastric cancer.
5-Fluorouracil is the first choice chemotherapeutic drug for patients with gastric cancer, but the mechanism that 5-fluorouracil plays the anti-tumor role remains unclear. The aim of this study was to clarify correlated [corrected] proteins induced by 5-fluorouracil in the apoptosis-initiation of human gastric cancer (MGC-803) cells. The time point of apoptosis-initiation induced by 5-fluorouracil in MGC-803 cells was determinated using 5-fluorouracil-withdrawal. Two-dimensional electrophoreses (2-DE) were employed to compare the differentials of protein expressions of the MGC-803 cells at the apoptosis-initiation phase and those of the MGC-803 cells untreated with 5-fluorouracil. The differential proteins included 14 upregulated proteins and 8 downregulated proteins. They indicated a more-than-doubled alteration. These proteins were digested in gels by trypsin and the mass of generated peptides were measured by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The data obtained from peptide mass fingerprinting (PMF) were searched out using the internet available database mascot (http://www.matrixscience.com). The results showed that proteomics analyses have evidenced that many kinds of proteins are involved in the apoptosis initiation of human gastric cancer MGC-803 cells. These proteins are related to metabolism, oxidation, cytoskeleton and signal transduction and other aspects of cells. In conclusion, the experiment model of apoptosis-initiation of human gastric cancer MGC-803 cells induced by 5-fluorouracil based on proteomic analysis has been established, giving an impetus to researches of the mechanism of apoptosis in human gastric cancer, and laying a foundation for the selection of potential drug precursors specific for inducing apoptosis-initiation in human gastric cancer.
Chen
Chun-Yan
CY
Department of Microbiology, School of Medicine, Shandong University, Jinan 250012, Shandong, PR China.
Jia
Ji-Hui
JH
Zhang
Mao-Xiu
MX
Zhou
Ya-Bin
YB
Zhang
Rong-Mei
RM
Yu
Xiu-Ping
XP
D000230:Adenocarcinoma / Q000188:drug therapy / Q000503:physiopathology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D005472:Fluorouracil / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D040901:Proteomics; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000503:physiopathology*
D005472:Fluorouracil