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Article

Effect of Smad3/4 on chemotherapeutic drug sensitivity in colorectal cancer cells

  • Authors:
    • Sung Ung Moon
    • Mi Hyun Kang
    • Ji Hea Sung
    • Jin Won Kim
    • Jeong Ok Lee
    • Yu Jung Kim
    • Keun Wook Lee
    • Soo Mee Bang
    • Jong Seok Lee
    • Jee Hyun Kim

  • View Affiliations / Copyright

    Affiliations: Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do 463-070, Republic of Korea
  • Pages: 185-192
    |
    Published online on: November 3, 2014
       https://doi.org/10.3892/or.2014.3582
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Abstract

Smad3 and Smad4 are signaling mediators in the transforming growth factor β (TGFβ) pathway and play a major role in the progression and migration of many types of cancers. The TGFβ pathway is correlated with resistance against both targeted and conventional chemotherapeutic drugs. The aim of this study was to determine the effect of Smad3/4 on drug sensitivity in chemotherapy-resistant colorectal cancer (CRC) cells. We isolated the TGFβ-mediated chemoresistant CRC cell line DLD1-5FU-C10, which showed high expression of Smad3/4 and p21. In order to analyze the influence of Smad3/4 on drug sensitivity in DLD1-5FU-C10 cells, we knocked down Smad3/4 using small interfering RNAs (siRNA). The results showed similar drug sensitivity between the DLD1‑5FU-C10 and the DLD1 control cells and reduced p21 expression. In addition, we found a significant increase in the levels of 3 TGFβ downstream factors: interleukin 6 (IL6), plasminogen activator (PLAU) and prostaglandin-endoperoxide synthase 2 (PTGS2). Furthermore, we showed that Smad3/4 regulated the JAK1/STAT3 pathway via IL6 in the chemoresistant CRC cell line. In conclusion, we identified Smad3/4 as a novel drug sensitivity regulator in TGFβ-mediated chemotherapy-resistant CRC cells. Our results suggest that Smad3/4 regulate p-STAT3 signaling by IL6 and p21 and highlight an important role for STAT3 signaling in Smad3/4 regulated drug sensitivity in chemoresistant CRC cells.
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Copy and paste a formatted citation
Spandidos Publications style
Moon SU, Kang MH, Sung JH, Kim JW, Lee JO, Kim YJ, Lee KW, Bang SM, Lee JS, Kim JH, Kim JH, et al: Effect of Smad3/4 on chemotherapeutic drug sensitivity in colorectal cancer cells. Oncol Rep 33: 185-192, 2015.
APA
Moon, S.U., Kang, M.H., Sung, J.H., Kim, J.W., Lee, J.O., Kim, Y.J. ... Kim, J.H. (2015). Effect of Smad3/4 on chemotherapeutic drug sensitivity in colorectal cancer cells. Oncology Reports, 33, 185-192. https://doi.org/10.3892/or.2014.3582
MLA
Moon, S. U., Kang, M. H., Sung, J. H., Kim, J. W., Lee, J. O., Kim, Y. J., Lee, K. W., Bang, S. M., Lee, J. S., Kim, J. H."Effect of Smad3/4 on chemotherapeutic drug sensitivity in colorectal cancer cells". Oncology Reports 33.1 (2015): 185-192.
Chicago
Moon, S. U., Kang, M. H., Sung, J. H., Kim, J. W., Lee, J. O., Kim, Y. J., Lee, K. W., Bang, S. M., Lee, J. S., Kim, J. H."Effect of Smad3/4 on chemotherapeutic drug sensitivity in colorectal cancer cells". Oncology Reports 33, no. 1 (2015): 185-192. https://doi.org/10.3892/or.2014.3582
Copy and paste a formatted citation
x
Spandidos Publications style
Moon SU, Kang MH, Sung JH, Kim JW, Lee JO, Kim YJ, Lee KW, Bang SM, Lee JS, Kim JH, Kim JH, et al: Effect of Smad3/4 on chemotherapeutic drug sensitivity in colorectal cancer cells. Oncol Rep 33: 185-192, 2015.
APA
Moon, S.U., Kang, M.H., Sung, J.H., Kim, J.W., Lee, J.O., Kim, Y.J. ... Kim, J.H. (2015). Effect of Smad3/4 on chemotherapeutic drug sensitivity in colorectal cancer cells. Oncology Reports, 33, 185-192. https://doi.org/10.3892/or.2014.3582
MLA
Moon, S. U., Kang, M. H., Sung, J. H., Kim, J. W., Lee, J. O., Kim, Y. J., Lee, K. W., Bang, S. M., Lee, J. S., Kim, J. H."Effect of Smad3/4 on chemotherapeutic drug sensitivity in colorectal cancer cells". Oncology Reports 33.1 (2015): 185-192.
Chicago
Moon, S. U., Kang, M. H., Sung, J. H., Kim, J. W., Lee, J. O., Kim, Y. J., Lee, K. W., Bang, S. M., Lee, J. S., Kim, J. H."Effect of Smad3/4 on chemotherapeutic drug sensitivity in colorectal cancer cells". Oncology Reports 33, no. 1 (2015): 185-192. https://doi.org/10.3892/or.2014.3582
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