title: The kallikrein-related peptidase 13 (KLK13) gene is substantially up-regulated after exposure of gastric cancer cells to antineoplastic agents.
abstract: Gastric cancer constitutes one of the most common neoplasms globally. Kallikrein-related peptidases have attracted interest as potential tumor markers and future targets for novel cancer therapeutics. We have recently reported KLK13 clinical importance as a favorable prognostic biomarker for gastric cancer patients' survival. By aiming to explore how the molecular profile of KLK13 is modified in stomach cancer cells treated with antineoplastic drugs, we examined, for the first time, the mRNA alterations of this gene following gastric cancer cells' exposure to the prominent chemotherapeutic substances epirubicin, oxaliplatin, or methotrexate. The antiproliferative effects of these agents, on AGS cells' growth, were determined by the 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide and trypan blue assays. Total RNA, isolated from the harvested cells, was reverse-transcribed to cDNA. KLK13 levels were quantified via real-time PCR using the SYBR Green chemistry. The relative changes of KLK13 expression were calculated with the comparative C (t) (2(-ddCt)) method. Distinct KLK13 profiles resulted from AGS cells' incubation with epirubicin or methotrexate for 24, 36, and 48 h. KLK13 expression increased in a time-dependent manner up to 5.70 times (for epirubicin) or 5.76 times (for methotrexate) at 48 h compared with the corresponding untreated cells. According to our results, KLK13 expression is implicated in the molecular pathways that are triggered after administration of anticancer agents on gastric cancer cells. Moreover, our data support the possibility that KLK13 may be exploited as a future molecular predictor of gastric cancer cells' response to chemotherapy.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Athens, Panepistimiopolis, Athens 15701, Greece.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Florou
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Mavridis
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
mesh_terms: D000230:Adenocarcinoma; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D015251:Epirubicin / Q000494:pharmacology*; D006801:Humans; D007610:Kallikreins / Q000235:genetics* / Q000378:metabolism; D008727:Methotrexate / Q000494:pharmacology*; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D012333:RNA, Messenger; D000077150:Oxaliplatin; D015251:Epirubicin; C470778:KLK13 protein, human; D007610:Kallikreins; D008727:Methotrexate