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. 1x10(4) 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 2.5-1000 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-3beta and phospho-GSK-3beta 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-3beta (ser9) 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-3beta, and the activation of TP53INP1 and pospho-GSK-3beta (ser9).
AIM: To investigate the expression of genes involved in the gemcitabine-induced cytotoxicity in humanpancreatic cancer cells. METHODS: A humanpancreatic cancer cell line, PANC-1, was cultured. 1x10(4) 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 2.5-1000 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-3beta and phospho-GSK-3beta 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-3beta (ser9) 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-3beta, and the activation of TP53INP1 and pospho-GSK-3beta (ser9).
Authors: H A Burris; M J Moore; J Andersen; M R Green; M L Rothenberg; M R Modiano; M C Cripps; R K Portenoy; A M Storniolo; P Tarassoff; R Nelson; F A Dorr; C D Stephens; D D Von Hoff Journal: J Clin Oncol Date: 1997-06 Impact factor: 44.544
Authors: Y Motoo; Y Satomura; I Mouri; H Mouri; K Ohtsubo; J Sakai; T Fujii; H Taga; Y Yamaguchi; H Watanabe; T Okai; N Sawabu Journal: Dig Dis Sci Date: 1999-06 Impact factor: 3.199
Authors: D Malka; S Vasseur; H Bödeker; E M Ortiz; N J Dusetti; P Verrando; J C Dagorn; J L Iovanna Journal: Gastroenterology Date: 2000-09 Impact factor: 22.682
Authors: D Taïeb; S Giusiano; F Sebag; M Marcy; C de Micco; F F Palazzo; N J Dusetti; J L Iovanna; J F Henry; S Garcia; Colette Taranger-Charpin Journal: World J Surg Date: 2010-04 Impact factor: 3.352
Authors: Yixing Jiang; Nicole A DiVittore; James M Kaiser; Sriram S Shanmugavelandy; Jennifer L Fritz; Yasser Heakal; Hephzibah Rani S Tagaram; Hua Cheng; Myles C Cabot; Kevin F Staveley-O'Carroll; Melissa A Tran; Todd E Fox; Brian M Barth; Mark Kester Journal: Cancer Biol Ther Date: 2011-10-01 Impact factor: 4.742
Authors: Linda Waldherr; Maria Seitanidou; Marie Jakešová; Verena Handl; Sophie Honeder; Marta Nowakowska; Tamara Tomin; Meysam Karami Rad; Tony Schmidt; Joachim Distl; Ruth Birner-Gruenberger; Gord von Campe; Ute Schäfer; Magnus Berggren; Beate Rinner; Martin Asslaber; Nassim Ghaffari-Tabrizi-Wizsy; Silke Patz; Daniel T Simon; Rainer Schindl Journal: Adv Mater Technol Date: 2021-04-12