CDK inhibitor enhances the sensitivity to 5-fluorouracil in colorectal cancer cells

  • Authors:
    • Koichi Takagi
    • Yoshihiro Sowa
    • Ozgur Muhammer Cevik
    • Ryoko Nakanishi
    • Toshiyuki Sakai
  • View Affiliations

  • Published online on: May 1, 2008     https://doi.org/10.3892/ijo.32.5.1105
  • Pages: 1105-1110
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Thymidylate synthase (TS) is a dNTP synthetic enzyme and is also a target enzyme of 5-fluorouracil (5-FU). 5-FU is one of the anticancer agents most frequently used for the treatment of colorectal cancers. However, the clinical rate of response to its use as a single agent is not exceptionally high. Therefore, various combination chemotherapies have been devised. The elevated expression of TS in cancer cells is a serious obstacle in the clinical use of 5-FU. In the present study, TS expression was up-regulated by the knockout of the p21WAF1/CIP1 gene in human colorectal cancer HCT116 cells, suggesting that TS expression is mediated through the inhibition of cyclin-dependent kinase (CDK). Based on these findings, we tested whether the CDK inhibitor (CDKI) SU9516, acted as a suppressor of TS. SU9516 effectively reduced the expression of TS in a dose-dependent manner. Furthermore, the reduction of TS expression resulted in enhancement of the sensitivity to 5-FU in human colon cancer DLD-1 cells. Thus, SU9516 might be a promising compound for combination chemotherapy with 5-FU.

Related Articles

Journal Cover

May 2008
Volume 32 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Takagi, K., Sowa, Y., Cevik, O.M., Nakanishi, R., & Sakai, T. (2008). CDK inhibitor enhances the sensitivity to 5-fluorouracil in colorectal cancer cells. International Journal of Oncology, 32, 1105-1110. https://doi.org/10.3892/ijo.32.5.1105
MLA
Takagi, K., Sowa, Y., Cevik, O. M., Nakanishi, R., Sakai, T."CDK inhibitor enhances the sensitivity to 5-fluorouracil in colorectal cancer cells". International Journal of Oncology 32.5 (2008): 1105-1110.
Chicago
Takagi, K., Sowa, Y., Cevik, O. M., Nakanishi, R., Sakai, T."CDK inhibitor enhances the sensitivity to 5-fluorouracil in colorectal cancer cells". International Journal of Oncology 32, no. 5 (2008): 1105-1110. https://doi.org/10.3892/ijo.32.5.1105