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Epithelial-mesenchymal Transition is Associated with Acquired Resistance to 5-Fluorocuracil in HT-29 Colon Cancer Cells.

Kim AY, Kwak JH, Je NK, Lee YH, Jung YS - Toxicol Res (2015)

Bottom Line: Of interest, we also found a marked increase in the expression of EMT-inducing transcription factors Twist, Zeb1, and Zeb2.Taken together, these results indicate that EMT could be associated with 5-FU resistance acquired by HT-29 cells.A specific role of each transcription factor found in this study will require further investigation.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Pusan National University, Busan, Korea.

ABSTRACT
5-Fluorouracil (5-FU) is commonly used for the therapy of colon cancer; however, acquired resistance to 5-FU is a critical barrier to successful treatment and the primary cause of chemotherapy failure. Epithelialmesenchymal transition (EMT) is a process whereby cells undergo alterations in morphology and molecular characteristics promoting tumor progression and metastasis. Accumulating evidence shows that transition from epithelial to mesenchymal phenotype in cancer cells is associated with their resistance to chemotherapy. However, it is still poorly understood whether EMT is involved in acquired resistance to 5-FU. In this study, we developed an in vitro cell model, 5-FU-resistant HT-29 colon cancer cells, and characterized the differences in cellular morphology and molecular alterations between parental and resistant cells. In accord with mesenchymal-like morphology of 5-FU-resistant HT-29 cells, the expression of the mesenchymal marker fibronectin was significantly increased in these cells in comparision with that in the parental cells. Of interest, we also found a marked increase in the expression of EMT-inducing transcription factors Twist, Zeb1, and Zeb2. Finally, 5-FU-resistant cells showed enhanced migration in comparison with parental HT-29. Taken together, these results indicate that EMT could be associated with 5-FU resistance acquired by HT-29 cells. A specific role of each transcription factor found in this study will require further investigation.

No MeSH data available.


Related in: MedlinePlus

5-FU resistant phenotype exhibits an EMT-like cellular characteristics compared with parental HT-29 cells. (A) Protein expression of E-cadherin and fibronection were determined by western blotting. (B) Density of each blot was quantified using Image J. Each value represents the mean ± SD of three independent experiments. *, **Significantly different from the parental HT-29 cells at p < 0.05, 0.01, respectively (Student’s t-test).
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Figure 002: 5-FU resistant phenotype exhibits an EMT-like cellular characteristics compared with parental HT-29 cells. (A) Protein expression of E-cadherin and fibronection were determined by western blotting. (B) Density of each blot was quantified using Image J. Each value represents the mean ± SD of three independent experiments. *, **Significantly different from the parental HT-29 cells at p < 0.05, 0.01, respectively (Student’s t-test).

Mentions: Cells with 5-FU-resistant phenotype exhibit EMT-like characteristics in comparison with the phenotype of parental HT-29 cells. The observed morphological changes implied that the 5-FU-resistant cells had transitioned to a mesenchymal phenotype. To determine whether these morphological changes were associated with EMT, we examined the expression of epithelial and mesenchymal marker proteins. Consistent with morphological changes, 5-FU-resistant cells showed down-regulation of the epithelial marker E-cadherin and up-regulation of the mesenchymal marker fibronectin (Fig. 2). These results suggest that EMT could be associated with acquired drug resistance after long-term exposure to 5-FU.


Epithelial-mesenchymal Transition is Associated with Acquired Resistance to 5-Fluorocuracil in HT-29 Colon Cancer Cells.

Kim AY, Kwak JH, Je NK, Lee YH, Jung YS - Toxicol Res (2015)

5-FU resistant phenotype exhibits an EMT-like cellular characteristics compared with parental HT-29 cells. (A) Protein expression of E-cadherin and fibronection were determined by western blotting. (B) Density of each blot was quantified using Image J. Each value represents the mean ± SD of three independent experiments. *, **Significantly different from the parental HT-29 cells at p < 0.05, 0.01, respectively (Student’s t-test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4505345&req=5

Figure 002: 5-FU resistant phenotype exhibits an EMT-like cellular characteristics compared with parental HT-29 cells. (A) Protein expression of E-cadherin and fibronection were determined by western blotting. (B) Density of each blot was quantified using Image J. Each value represents the mean ± SD of three independent experiments. *, **Significantly different from the parental HT-29 cells at p < 0.05, 0.01, respectively (Student’s t-test).
Mentions: Cells with 5-FU-resistant phenotype exhibit EMT-like characteristics in comparison with the phenotype of parental HT-29 cells. The observed morphological changes implied that the 5-FU-resistant cells had transitioned to a mesenchymal phenotype. To determine whether these morphological changes were associated with EMT, we examined the expression of epithelial and mesenchymal marker proteins. Consistent with morphological changes, 5-FU-resistant cells showed down-regulation of the epithelial marker E-cadherin and up-regulation of the mesenchymal marker fibronectin (Fig. 2). These results suggest that EMT could be associated with acquired drug resistance after long-term exposure to 5-FU.

Bottom Line: Of interest, we also found a marked increase in the expression of EMT-inducing transcription factors Twist, Zeb1, and Zeb2.Taken together, these results indicate that EMT could be associated with 5-FU resistance acquired by HT-29 cells.A specific role of each transcription factor found in this study will require further investigation.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Pusan National University, Busan, Korea.

ABSTRACT
5-Fluorouracil (5-FU) is commonly used for the therapy of colon cancer; however, acquired resistance to 5-FU is a critical barrier to successful treatment and the primary cause of chemotherapy failure. Epithelialmesenchymal transition (EMT) is a process whereby cells undergo alterations in morphology and molecular characteristics promoting tumor progression and metastasis. Accumulating evidence shows that transition from epithelial to mesenchymal phenotype in cancer cells is associated with their resistance to chemotherapy. However, it is still poorly understood whether EMT is involved in acquired resistance to 5-FU. In this study, we developed an in vitro cell model, 5-FU-resistant HT-29 colon cancer cells, and characterized the differences in cellular morphology and molecular alterations between parental and resistant cells. In accord with mesenchymal-like morphology of 5-FU-resistant HT-29 cells, the expression of the mesenchymal marker fibronectin was significantly increased in these cells in comparision with that in the parental cells. Of interest, we also found a marked increase in the expression of EMT-inducing transcription factors Twist, Zeb1, and Zeb2. Finally, 5-FU-resistant cells showed enhanced migration in comparison with parental HT-29. Taken together, these results indicate that EMT could be associated with 5-FU resistance acquired by HT-29 cells. A specific role of each transcription factor found in this study will require further investigation.

No MeSH data available.


Related in: MedlinePlus