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Article

Foxp3 overexpression decreases sensitivity to chemotherapy in mouse Lewis lung cancer cells

  • Authors:
    • Chun Li
    • Wei Yang
    • Xiaodong Gai
    • Yinglin Zhang
    • Yi Li
    • Haiying Fu
  • View Affiliations / Copyright

    Affiliations: Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin, P.R. China, Department of Immunology, School of Basic Medical Sciences, Beihua University, Jilin, P.R. China
  • Pages: 977-982
    |
    Published online on: September 5, 2012
       https://doi.org/10.3892/mmr.2012.1066
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Abstract

Chemotherapy is the main strategy for the treatment of lung cancer. However, sensitivity to chemotherapy, one of the main factors affecting the survival rate of patients with lung cancer, is extremely poor. Forkhead box P3 (Foxp3) is the key regulatory gene for the development and function of CD4+CD25+ regulatory T cells (Tregs). Increased levels of Tregs and Foxp3 expression in the peripheral blood and tumour specimens of cancer patients are associated with tumour progression and poor prognosis. In addition, certain studies have suggested that Tregs may be resistant to conventional chemotherapy and thus, enhance tumour immune evasion. Previous studies have demonstrated that Foxp3 is also expressed within tumour cells and that it may mimic the function of Tregs. Currently, the correlation between the tumour cell expression of Foxp3 and sensitivity to chemotherapy is unclear. Therefore, it was hypothesised that Foxp3 causes resistance to chemotherapeutic agents in lung cancer cells and that it may consequently promote the progression of lung cancer. In the current study, the expression of Foxp3 in mouse Lewis lung cancer (LLC) cells was detected using RT-PCR and immunocytochemistry. The overexpression of Foxp3, which was accomplished by the transient transfection of recombinant pcDNA3.1-Foxp3 or empty plasmids into LLC cells, was confirmed by RT-PCR and western blot analysis. The inhibition of cell proliferation was measured using MTT assay. The expression of multidrug resistance protein 1 (mdr1) mRNA and its protein product, P-glycoprotein (P-gp), were detected by RT-PCR and flow cytometry, respectively. The results revealed that Foxp3 was expressed by LLC cells. The inhibitory rate of cell proliferation in Foxp3-overexpressing LLC cells compared with those transfected with an empty plasmid was significantly decreased following adriamycin (ADM) and mitomycin C (MMC) treatment. The IC50 values of ADM and MMC in Foxp3-overexpressing LLC cells were increased. The expression levels of mdr1 mRNA and P-gp were significantly upregulated in Foxp3 overexpressing LLC cells. These results suggest that Foxp3 reduces the sensitivity of LLC cells to ADM and MMC, thus promoting tumour progression, by upregulating the expression of mdr1 mRNA and P-gp.
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1 

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T and Thun MJ: Cancer statistics. CA Cancer J Clin. 58:71–96. 2008.

2 

Hori S, Nomura T and Sakaguchi S: Control of regulatory T cell development by the transcription factor Foxp3. Science. 299:1057–1061. 2003. View Article : Google Scholar : PubMed/NCBI

3 

Fontenot JD, Rasmussen JP, Williams LM, Dooley JL, Farr AG and Rudensky AY: Regulatory T cell lineage specification by the forkhead transcription factor Foxp3. Immunity. 22:329–341. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Woo EY, Yeh H, Chu CS, Schlienger K, Carroll RG, Riley JL, Kaiser LR and June CH: Cutting edge: regulatory T cells from lung patients directly inhibit autologous T cell proliferation. J Immunol. 168:4272–4276. 2002. View Article : Google Scholar : PubMed/NCBI

5 

Schneider T, Kimpfler S, Warth A, Schnabel PA, Dienemann H, Schadendorf D, Hoffmann H and Umansky V: Foxp3+ regulatory T cells and killer cells distinctly infiltrate primary tumors and draining lymph nodes in pulmonary adenocarcinoma. J Thorac Oncol. 6:432–438. 2011.

6 

Shimizu K, Nakata M, Hirami Y, Yukawa T, Maeda A and Tanemoto K: Tumor-infiltrating Foxp3+ regulatory T cells are correlated with cyclooxygenase-2 expression and are associated with recurrence in resected non-small cell lung cancer. J Thorac Oncol. 5:585–590. 2010.

7 

Tokuno K, Hazama S, Yoshino S, Yoshida S and Oka M: Increased prevalence of regulatory T-cells in the peripheral blood of patients with gastrointestinal cancer. Anticancer Res. 29:1527–1532. 2009.PubMed/NCBI

8 

Deng L, Zhang H, Luan Y, Zhang J, Xing Q, Dong S, Wu X, Liu M and Wang S: Accumulation of foxp3+ T regulatory cells in draining lymph nodes correlates with disease progression and immune suppression in colorectal cancer patients. Clin Cancer Res. 16:4105–4112. 2010.

9 

Petersen RP, Campa MJ, Sperlazza J, et al: Tumor infiltrating Foxp3+ regulatory T-cells are associated with recurrence in pathologic stage I NSCLC patients. Cancer. 107:2866–2872. 2006.PubMed/NCBI

10 

Hinz S, Pagerols-Raluy L, Oberg HH, et al: Foxp3 expression in pancreatic carcinoma cells as a novel mechanism of immune evasion in cancer. Cancer Res. 67:8344–8350. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Zuo T, Liu R, Zhang H, Chang X and Liu Y, Wang L, Zheng P and Liu Y: FOXP3 is a novel transcriptional repressor for the breast cancer oncogene SKP2. J Clin Invest. 117:3765–3773. 2007.PubMed/NCBI

12 

Merlo A, Casalini P, Carcangiu ML, Malventano C, Triulzi T, Mènard S, Tagliabue E and Balsari A: FOXP3 expression and overall survival in breast cancer. J Clin Oncol. 27:1746–1752. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Wang LH, Su L and Wang JT: Correlation between elevated FOXP3 expression and increased lymph node metastasis of gastric cancer. Chin Med J (Engl). 123:3545–3549. 2010.PubMed/NCBI

14 

Wang G, Liu G, Liu Y, Li X and Su Z: FOXP3 expression in esophageal cancer cells is associated with poor prognosis in esophageal cancer. Hepatogastroenterology. 59:Mar 2–2012.(Epub ahead of print). View Article : Google Scholar

15 

Szczepanski MJ, Szajnik M, Czystowska M, et al: Increased frequency and suppression by regulatory T cells in patients with acute myelogenous leukemia. Clin Cancer Res. 15:3325–3332. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Xu H, Mao Y, Dai Y, Wang Q and Zhang X: CD4+CD25+ regulatory T cells in patients with advanced gastrointestinal cancer treated with chemotherapy. Onkologie. 32:246–252. 2009.

17 

Ruan Q, Kameswaran V, Tone Y, Li L, Liou HC, Greene MI, Tone M and Chen YH: Development of Foxp3+ regulatory T cells is driven by A c-Rel enhanceosome. Immunity. 31:932–940. 2009.PubMed/NCBI

18 

Melaine N, Liénard MO, Dorval I, Le Goascogne C, Lejeune H and Jégou B: Multidrug resistance genes and p-glycoprotein in the testis of the rat, mouse, Guinea pig, and human. Biol Reprod. 67:1699–1707. 2002. View Article : Google Scholar : PubMed/NCBI

19 

Simeone L, Straubinger M, Khan MA, Nalleweg N, Cheusova T and Hashemolhosseini S: Identification of Erbin interlinking MuSK and ErbB2 and its impact on acetylcholine receptor aggregation at the neuromuscular junction. J Neurosci. 30:6620–6634. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Shim GS, Manandhar S, Shin DH, Kim TH and Kwak MK: Acquisition of doxorubicin resistance in ovarian carcinoma cells accompanies activation of the NRF2 pathway. Free Radic Biol Med. 47:1619–1631. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Widmer N, Colombo S, Buclin T and Decosterd LA: Functional consequence of MDR1 expression on imatinib intracellular concentrations. Blood. 102:11422003. View Article : Google Scholar : PubMed/NCBI

22 

Aller SG, Yu J, Ward A, et al: Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science. 323:1718–1722. 2009. View Article : Google Scholar : PubMed/NCBI

23 

Loo TW and Clarke DM: Location of the rhodamine-binding site in the human multidrug resistance P-glycoprotein. J Biol Chem. 277:44332–44338. 2002. View Article : Google Scholar : PubMed/NCBI

24 

Ambudkar SV, Kim IW and Sauna ZE: The power of the pump: mechanisms of action of P-glycoprotein (ABCB1). Eur J Pharm Sci. 27:392–400. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Szachowicz-Petelska B, Figaszewski Z and Lewandowski W: Mechanisms of transport across cell membranes of complexes contained in antitumour drugs. Int J Pharm. 222:169–182. 2001. View Article : Google Scholar : PubMed/NCBI

26 

Pires MM, Emmert D, Hrycyna CA and Chmielewski J: Inhibition of P-glycoprotein-mediated paclitaxel resistance by reversibly linked quinine homodimers. Mol Pharmacol. 75:92–100. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Enokida H, Gotanda T, Oku S, et al: Reversal of P-glycoprotein mediated paclitaxel resistance by new synthetic isoprenoids in human bladder cancer cell line. Jpn J Cancer Res. 93:1037–1046. 2002. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Li C, Yang W, Gai X, Zhang Y, Li Y and Fu H: Foxp3 overexpression decreases sensitivity to chemotherapy in mouse Lewis lung cancer cells. Mol Med Rep 6: 977-982, 2012.
APA
Li, C., Yang, W., Gai, X., Zhang, Y., Li, Y., & Fu, H. (2012). Foxp3 overexpression decreases sensitivity to chemotherapy in mouse Lewis lung cancer cells. Molecular Medicine Reports, 6, 977-982. https://doi.org/10.3892/mmr.2012.1066
MLA
Li, C., Yang, W., Gai, X., Zhang, Y., Li, Y., Fu, H."Foxp3 overexpression decreases sensitivity to chemotherapy in mouse Lewis lung cancer cells". Molecular Medicine Reports 6.5 (2012): 977-982.
Chicago
Li, C., Yang, W., Gai, X., Zhang, Y., Li, Y., Fu, H."Foxp3 overexpression decreases sensitivity to chemotherapy in mouse Lewis lung cancer cells". Molecular Medicine Reports 6, no. 5 (2012): 977-982. https://doi.org/10.3892/mmr.2012.1066
Copy and paste a formatted citation
x
Spandidos Publications style
Li C, Yang W, Gai X, Zhang Y, Li Y and Fu H: Foxp3 overexpression decreases sensitivity to chemotherapy in mouse Lewis lung cancer cells. Mol Med Rep 6: 977-982, 2012.
APA
Li, C., Yang, W., Gai, X., Zhang, Y., Li, Y., & Fu, H. (2012). Foxp3 overexpression decreases sensitivity to chemotherapy in mouse Lewis lung cancer cells. Molecular Medicine Reports, 6, 977-982. https://doi.org/10.3892/mmr.2012.1066
MLA
Li, C., Yang, W., Gai, X., Zhang, Y., Li, Y., Fu, H."Foxp3 overexpression decreases sensitivity to chemotherapy in mouse Lewis lung cancer cells". Molecular Medicine Reports 6.5 (2012): 977-982.
Chicago
Li, C., Yang, W., Gai, X., Zhang, Y., Li, Y., Fu, H."Foxp3 overexpression decreases sensitivity to chemotherapy in mouse Lewis lung cancer cells". Molecular Medicine Reports 6, no. 5 (2012): 977-982. https://doi.org/10.3892/mmr.2012.1066
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