title: Resistance of colorectal cancer cells to radiation and 5-FU is associated with MELK expression.
abstract: It was reported that the local recurrence would be caused by cancer stem cells acquiring chemo- and radio-resistance. Recently, one of the potential therapeutic targets for colorectal and other cancers has been identified, which is maternal embryonic leucine zipper kinase (MELK). MELK is known as an embryonic and neural stem cell marker, and associated with the cell survival, cell proliferation, and apoptosis. In this study, SNU-503, which is a rectal cancer cell line, was treated with radiation or 5-fluorouracil (5-FU), and elevation of the MELK expression level was observed. Furthermore, the cell line was pre-treated with small interfering RNA (siRNA) against MELK mRNA before treatment of radiation or 5-FU and its effects on cell cycle and proliferation were observed. We demonstrated that knockdown of MELK reduced the proliferation of cells with radiation or 5-FU treatment. In addition, MELK suppression caused changes in cell cycle. In conclusion, MELK could be associated with increased resistance of colorectal cancer cells against radiation and 5-FU.
authors.affiliation: Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Seungho
authors.initials: S
authors.lastname: Choi
authors.forename: Ja-Lok
authors.initials: JL
authors.lastname: Ku
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000201:enzymology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005472:Fluorouracil / Q000494:pharmacology*; D005720:Gamma Rays; D055785:Gene Knockdown Techniques; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*
chemical_list: D000964:Antimetabolites, Antineoplastic; D034741:RNA, Small Interfering; C484610:MELK protein, human; D017346:Protein Serine-Threonine Kinases; D005472:Fluorouracil