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Article

Overexpression of CD133 enhances chemoresistance to 5-fluorouracil by activating the PI3K/Akt/p70S6K pathway in gastric cancer cells

  • Authors:
    • Youlong Zhu
    • Jiwei Yu
    • Shoulian Wang
    • Ruiqi  Lu
    • Jugang Wu
    • Bojian Jiang
  • View Affiliations / Copyright

    Affiliations: Department of First General Surgery, Shanghai Third People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201900, P.R. China
  • Pages: 2437-2444
    |
    Published online on: September 17, 2014
       https://doi.org/10.3892/or.2014.3488
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Abstract

CD133 has been reported to be associated with chemoresistance in various cancer cells. The efficacy of 5-fluorouracil (5-FU), an important chemotherapeutic agent for advanced gastric cancer (GC), is limited by 5-FU resistance. Hence, the present study investigated the function of CD133 in 5-FU resistance in human GC cells. We isolated CD133+ GC cells by immunomagnetic cell sorting and CD133 expression was modulated by transfection of CD133 gene or CD133 small interfering ribonucleic acid. To assess the 5-FU cytotoxicity, Cell Counting Kit-8 was used. Expression of CD133, P-glycoprotein (P-gp), B-cell lymphoma 2 (Bcl‑2), Bcl-2-associated X protein (Bax), phospho-Akt (p-Akt) and phospho-p70S6 kinase (p-p70S6K) were analyzed by western blotting. CD133, P-gp, Bcl-2 and Bax messenger ribonucleic acids were evaluated using semi-quantitative reverse transcriptase-polymerase chain reaction. Cell apoptosis was assessed by Hoechst 33258 staining. CD133+ cells were more resistant to 5-FU than CD133- cells, and showed higher expression of P-gp and Bcl-2 with lower expression of Bax. Furthermore, CD133 silencing enhanced 5-FU cytotoxicity and apoptotic characteristics, whereas CD133 overexpression increased 5-FU resistance. CD133 silencing and activation directly decreased and increased the expression of P-gp, Bcl‑2, p-Akt and p-p70S6K, respectively. Notably, Akt inhibition by LY294002 restored the 5-FU cytotoxicity suppressed by CD133 overexpression, while Akt activation by epidermal growth factor reversed the 5-FU cytotoxicity enhanced by CD133 silencing. Therefore, CD133 may inhibit 5-FU-induced apoptosis by regulating the expression of P-gp and Bcl-2 family mediated by phosphoinositide 3-kinase/Akt/p70S6K pathway in GC cells.
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Copy and paste a formatted citation
Spandidos Publications style
Zhu Y, Yu J, Wang S, Lu R, Wu J and Jiang B: Overexpression of CD133 enhances chemoresistance to 5-fluorouracil by activating the PI3K/Akt/p70S6K pathway in gastric cancer cells. Oncol Rep 32: 2437-2444, 2014.
APA
Zhu, Y., Yu, J., Wang, S., Lu, R., Wu, J., & Jiang, B. (2014). Overexpression of CD133 enhances chemoresistance to 5-fluorouracil by activating the PI3K/Akt/p70S6K pathway in gastric cancer cells. Oncology Reports, 32, 2437-2444. https://doi.org/10.3892/or.2014.3488
MLA
Zhu, Y., Yu, J., Wang, S., Lu, R., Wu, J., Jiang, B."Overexpression of CD133 enhances chemoresistance to 5-fluorouracil by activating the PI3K/Akt/p70S6K pathway in gastric cancer cells". Oncology Reports 32.6 (2014): 2437-2444.
Chicago
Zhu, Y., Yu, J., Wang, S., Lu, R., Wu, J., Jiang, B."Overexpression of CD133 enhances chemoresistance to 5-fluorouracil by activating the PI3K/Akt/p70S6K pathway in gastric cancer cells". Oncology Reports 32, no. 6 (2014): 2437-2444. https://doi.org/10.3892/or.2014.3488
Copy and paste a formatted citation
x
Spandidos Publications style
Zhu Y, Yu J, Wang S, Lu R, Wu J and Jiang B: Overexpression of CD133 enhances chemoresistance to 5-fluorouracil by activating the PI3K/Akt/p70S6K pathway in gastric cancer cells. Oncol Rep 32: 2437-2444, 2014.
APA
Zhu, Y., Yu, J., Wang, S., Lu, R., Wu, J., & Jiang, B. (2014). Overexpression of CD133 enhances chemoresistance to 5-fluorouracil by activating the PI3K/Akt/p70S6K pathway in gastric cancer cells. Oncology Reports, 32, 2437-2444. https://doi.org/10.3892/or.2014.3488
MLA
Zhu, Y., Yu, J., Wang, S., Lu, R., Wu, J., Jiang, B."Overexpression of CD133 enhances chemoresistance to 5-fluorouracil by activating the PI3K/Akt/p70S6K pathway in gastric cancer cells". Oncology Reports 32.6 (2014): 2437-2444.
Chicago
Zhu, Y., Yu, J., Wang, S., Lu, R., Wu, J., Jiang, B."Overexpression of CD133 enhances chemoresistance to 5-fluorouracil by activating the PI3K/Akt/p70S6K pathway in gastric cancer cells". Oncology Reports 32, no. 6 (2014): 2437-2444. https://doi.org/10.3892/or.2014.3488
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