2. Academic Validation
  3. Dipeptidyl Peptidase 9 Increases Chemoresistance and is an Indicator of Poor Prognosis in Colorectal Cancer

Dipeptidyl Peptidase 9 Increases Chemoresistance and is an Indicator of Poor Prognosis in Colorectal Cancer

  • Ann Surg Oncol. 2020 Oct;27(11):4337-4347. doi: 10.1245/s10434-020-08729-7.
Kazuhiro Saso 1,  Norikatsu Miyoshi 2,  Shiki Fujino 1,  Masaru Sasaki 1,  Masayoshi Yasui 3,  Masayuki Ohue 3,  Takayuki Ogino 1,  Hidekazu Takahashi 1,  Mamoru Uemura 1,  Chu Matsuda 1,  Tsunekazu Mizushima 1,  Yuichiro Doki 1,  Hidetoshi Eguchi 1
Affiliations

Affiliations

  • 1 Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
  • 2 Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan. [email protected].
  • 3 Department of Surgery, Osaka International Cancer Institute, Osaka, Japan.
PMID: 32734369 DOI: 10.1245/s10434-020-08729-7
Abstract

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.

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