A pharmacoproteomics study of the cancer cell line EKVX using capillary-LC/MS/MS.
The chemotherapeutic agent camptothecin, 10-OH (CPT,10-OH), was shown to act synergistically with the epithelial growth factor receptor (EGFR) inhibitor (AG1478) against several transformed cell lines. To study the cellular response to these drugs, the non-small-cell lung carcinoma cell line, EKVX, was treated with these compounds either alone or in combination. We performed a proteomic analysis using capillary-HPLC coupled with electrospray ion trap mass spectrometry (capillary-LC-ESI/MS) of a tryptic digest to obtain a global protein profile of the EKVX cell line and identify changes in protein expression. The combination of AG1478 and CPT,10-OH showed synergistic cytotoxicity and also changed the expression of multiple proteins, while individual treatments showed a lesser effect on protein expression. Thus, the synergistic action of AG1478 and CPT,10-OH was reflected in altered protein profiles, showing that a proteomic analysis can serve to evaluate chemotherapeutic agents and their combinations.
Wang
Yonghui
Y
Barnett Institute, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, USA.
Dai
Zunyan
Z
Sadee
Wolfgang
W
Hancock
William S
WS
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D011506:Proteins / Q000032:analysis* / Q000235:genetics; D040901:Proteomics / Q000379:methods*; D011799:Quinazolines; D020539:Sequence Analysis, Protein / Q000379:methods; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D020032:Tyrphostins / Q000494:pharmacology
D000970:Antineoplastic Agents; D011506:Proteins; D011799:Quinazolines; D020032:Tyrphostins; C101044:RTKI cpd; D004815:Epidermal Growth Factor