Establishment and molecular profiling of a novel human pancreatic cancer panel for 5-FU.
Ten novel human pancreatic carcinoma cell lines (Sui65 through Sui74) were established from a transplantable pancreatic carcinoma cell line. All the cell lines resembled the original clinical carcinoma in terms of the morphological and biological features, presenting with genetic alterations such as point mutations of K-ras and p53, attenuation or lack of SMAD4 and p16 and other relevant cellular characteristics. Using this panel, we evaluated the effects of 5-FU in suppressing the proliferation of pancreatic carcinoma cells. When tested in vitro, although Sui72 was highly susceptible to 5-FU, the other cell lines were found to be resistant to the drug. When Sui72 and Sui70 were implanted subcutaneously in SCID mice followed by treatment with 5-FU, the drug was found to be effective against Sui72 but not Sui70, consistent with the results in vitro. In order to identify the molecular determinant for high sensitivity of Sui72 to 5-FU, we examined the mRNA expression levels of the metabolic enzymes of 5-FU. Decreased expression of DPYD was observed in Sui72 as compared with other cell lines (0.1 versus 0.6 +/- 0.5, 0.1-fold). It is believed that the novel cell lines established in the present study will be useful for analyzing the pattern of progression of pancreatic cancer and for evaluating the efficacy of anticancer agents.
Yanagihara
Kazuyoshi
K
Central Animal Laboratory, National Cancer Center Research Institute, Tokyo, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan. kyanagih@ncc.go.jp
Takigahira
Misato
M
Tanaka
Hiromi
H
Arao
Tokuzo
T
Aoyagi
Yasuyuki
Y
Oda
Tatsuya
T
Ochiai
Atsushi
A
Nishio
Kazuto
K
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology* / Q000627:therapeutic use; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D051379:Mice; D010190:Pancreatic Neoplasms / Q000188:drug therapy*
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil