@article{oai:kanazawa-u.repo.nii.ac.jp:00027404, author = {Jiang, Pei-Hong and Motoo, Yoshiharu and Sawabu, Norio and Minamoto, Toshinari}, issue = {10}, journal = {World Journal of Gastroenterology}, month = {Mar}, note = {Aim: To investigate the expression of genes involved in the gemcitabine-induced cytotoxicity in human pancreatic cancer cells. Methods: A human pancreatic cancer cell line, PANC-1, was cultured. 1 × 104 PANC-1 cells were plated in 96-well microtiter plates. After being incubated for 24 h, gemcitabine was added to the medium at concentrations ranging 2.5 -1 000 mg/L. The AlamarBlue dye method was used for cell growth analysis. DNA fragmentation was quantitatively assayed using a DNA fragmentation enzyme-linked immunosorbent assay (ELISA) kit. PAP and TP53INP1 mRNA expression was determined using the reverse transcription-polymerase chain reaction with semi-quantitative analysis. The expression of GSK-3β and phospho-GSK-3β proteins was examined with Western blot analysis. Results: The IC50 for the drug after a 48-h exposure to gemcitabine was 16 mg/L. The growth of PANC-1 cells was inhibited by gemcitabine in a concentration-dependent manner (P< 0.0001) and the cell growth was also inhibited throughout the time course (P<0.0001). The DNA fragmentation rate in the gemcitabine-treated group at 48 h was 44.7 %, whereas it was 25.3 % in the untreated group. The PAP mRNA expression was decreased after being treated with gemcitabine, whereas the TP53INP1 mRNA was increased by the gemcitabine treatment. Western blot analysis showed that phospho-GSK-3βser9 was induced by the gemcitabine treatment. Conclusion: Gemcitabine suppresses PANC-1 cell proliferation and induces apoptosis. Apoptosis is considered to be associated with the inhibition of PAP and GSK-3β, and the activation of TP53INP1 and pospho-GSK-3βser9. © 2006 The WJG Press. All rights reserved., 金沢大学がん研究所}, pages = {1597--1602}, title = {Effect of gemcitabine on the expression of apoptosis-related genes in human pancreatic cancer cells.}, volume = {12}, year = {2006} }