Characterization and drug sensitivity of four newly established colon adenocarcinoma cell lines to antifolate inhibitors of thymidylate synthase Journal Article

  

Authors:	Longo, G. S. A.; Izzo, J.; Gorlick, R.; Banerjee, D.; Jhanwar, S. C.; Bertino, J. R.
Article Title:	Characterization and drug sensitivity of four newly established colon adenocarcinoma cell lines to antifolate inhibitors of thymidylate synthase
Abstract:	Four new cell lines were established from the primary tumors of patients with untreated colorectal adenocarcinoma. Drug sensitivity and characterization of these cell lines was performed. Three of the four cell lines formed colonies in soft agar and all were tumorigenic in nude mice. The cell lines were morphologically similar but had differences in growth characteristics. Two of the cell lines, C18 (CCCL-4) and C29 (CCCL-6), had a longer doubling time compared with C85 (CCCL-1) and C86 (CCCL-2). The C18 and C29 cell lines had chromosome 17 abnormalities and evidence by immunohistochemistry of a mutant p53 and had decreased levels of thymidylate synthase and dihydrofolate reductase proteins, associated with decreased thymidylate synthase catalytic activity in C18 and no detectable activity in C29. Raltitrexed and GW1843U89 showed potent cytotoxic activity and all four cell lines displayed similar cytotoxicity to these folate thymidylate synthase inhibitors. The C18 and C29 cell lines were in general resistant to the other agents tested (methotrexate, 5-fluorouracil, nolatrexed) when compared with the C85 and C86 cell lines. These new cell lines may be useful for the study of colorectal adenocarcinoma and for evaluating new drugs or treatment schedules. Copyright © 2001 Cognizant Comm. Corp.
Keywords:	immunohistochemistry; genetics; comparative study; adenocarcinoma; mouse; animal; metabolism; animals; mice; cell division; antimetabolites, antineoplastic; colonic neoplasms; drug effect; drug resistance; drug screening; enzymology; pathology; drug resistance, neoplasm; tumor cells, cultured; xenograft model antitumor assays; protein p53; blotting, western; immunology; drug antagonism; kinetics; cell culture; nude mouse; mice, nude; colon tumor; western blotting; tumor suppressor protein p53; folic acid antagonist; thymidylate synthase; folic acid antagonists; antineoplastic antimetabolite; karyotyping; aneuploidy; colorectal; antifolate; tumor stem cell assay; chromosome banding; chromosome banding pattern; humans; human; article; thymidylale synthase
Journal Title:	Oncology Research
Volume:	12
Issue:	8
ISSN:	0965-0407
Publisher:	Cognizant Communication Corporation
Date Published:	2000-01-01
Start Page:	309
End Page:	314
Language:	English
PUBMED:	11589301
PROVIDER:	scopus
DOI:	10.3727/096504001108747756
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-0034578430&partnerID=40&md5=5bec4a36abaaeace381db53b4c224814
Notes:	Export Date: 18 November 2015 -- Source: Scopus

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