title: Foxp3 overexpression decreases sensitivity to chemotherapy in mouse             Lewis lung cancer cells.
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.
authors.affiliation: Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun, PR China.
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Gai
authors.forename: Yinglin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Haiying
authors.initials: H
authors.lastname: Fu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016685:Mitomycin / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D012333:RNA, Messenger; D016685:Mitomycin; D004317:Doxorubicin