BACKGROUND: In recent years, systemic chemotherapy has significantly improved the prognosis of metastatic colorectal cancer (CRC); however, different patients have different responses to chemotherapeutics. METHODS: Dipeptidyl peptidase 9 (DPP9) is an enzyme in the dipeptidyl peptidase IV family that has been reported to increase drug sensitivity in acute myeloid leukemia. In this study, we examined the relationship between DPP9 expression and the prognosis of patients with CRC, as well as the role of DPP9 in anticancer drug resistance. Moreover, the effects of the DPP9 inhibitors talabostat and vildagliptin in CRC cell lines and primary cultured cells were assessed. RESULTS: High expression of DPP9 was associated with worse prognosis in 196 patients with CRC. Cell viability was markedly inhibited in CRC cell lines transfected with DPP9 small interfering RNA or small hairpin RNA. Talabostat suppressed proliferation in CRC cell lines and primary cultured cells, and increased their sensitivity to chemotherapy. Vildagliptin, a DPP family inhibitor currently administered for diabetes, also increased the sensitivity of CRC cells to anticancer drugs. CONCLUSION: DPP9 was a poor prognostic factor for CRC and could be a new therapeutic target, while vildagliptin could be used as a repositioned drug for CRC treatment.
BACKGROUND: In recent years, systemic chemotherapy has significantly improved the prognosis of metastatic colorectal cancer (CRC); however, different patients have different responses to chemotherapeutics. METHODS:Dipeptidyl peptidase 9 (DPP9) is an enzyme in the dipeptidyl peptidase IV family that has been reported to increase drug sensitivity in acute myeloid leukemia. In this study, we examined the relationship between DPP9 expression and the prognosis of patients with CRC, as well as the role of DPP9 in anticancer drug resistance. Moreover, the effects of the DPP9 inhibitors talabostat and vildagliptin in CRC cell lines and primary cultured cells were assessed. RESULTS: High expression of DPP9 was associated with worse prognosis in 196 patients with CRC. Cell viability was markedly inhibited in CRC cell lines transfected with DPP9 small interfering RNA or small hairpin RNA. Talabostat suppressed proliferation in CRC cell lines and primary cultured cells, and increased their sensitivity to chemotherapy. Vildagliptin, a DPP family inhibitor currently administered for diabetes, also increased the sensitivity of CRC cells to anticancer drugs. CONCLUSION:DPP9 was a poor prognostic factor for CRC and could be a new therapeutic target, while vildagliptin could be used as a repositioned drug for CRC treatment.
Authors: Herbert Hurwitz; Louis Fehrenbacher; William Novotny; Thomas Cartwright; John Hainsworth; William Heim; Jordan Berlin; Ari Baron; Susan Griffing; Eric Holmgren; Napoleone Ferrara; Gwen Fyfe; Beth Rogers; Robert Ross; Fairooz Kabbinavar Journal: N Engl J Med Date: 2004-06-03 Impact factor: 91.245
Authors: Alberto F Sobrero; Joan Maurel; Louis Fehrenbacher; Werner Scheithauer; Yousif A Abubakr; Manfred P Lutz; M Eugenia Vega-Villegas; Cathy Eng; Ernst U Steinhauer; Jana Prausova; Heinz-Josef Lenz; Christophe Borg; Gary Middleton; Hendrik Kröning; Gabriele Luppi; Oliver Kisker; Angela Zubel; Christiane Langer; Justin Kopit; Howard A Burris Journal: J Clin Oncol Date: 2008-04-07 Impact factor: 44.544
Authors: Oguz Bolgi; Maria Silva-Garcia; Breyan Ross; Esther Pilla; Vijayalakshmi Kari; Markus Killisch; Melanie Spitzner; Nadine Stark; Christof Lenz; Konstantin Weiss; Laura Donzelli; Mark D Gorrell; Marian Grade; Jan Riemer; Henning Urlaub; Matthias Dobbelstein; Robert Huber; Ruth Geiss-Friedlander Journal: EMBO Rep Date: 2022-08-01 Impact factor: 9.071