C-fos upregulates P-glycoprotein, contributing to the development of multidrug resistance in HEp-2 laryngeal cancer cells with VCR-induced resistance
Abstract Background Laryngeal cancer tends to have a very poor prognosis due to the unsatisfactory efficacy of chemotherapy for this cancer. Multidrug resistance (MDR) is the main cause of chemotherapy failure. The proto-oncogene c-fos has been shown to be involved in the development of MDR in sever...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-02-01
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| Series: | Cellular & Molecular Biology Letters |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s11658-017-0067-8 |
| _version_ | 1818612679412023296 |
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| author | Guodong Li Xiaoling Hu Lu Sun Xin Li Jianfeng Li Tongli Li Xiaohui Zhang |
| author_facet | Guodong Li Xiaoling Hu Lu Sun Xin Li Jianfeng Li Tongli Li Xiaohui Zhang |
| author_sort | Guodong Li |
| collection | DOAJ |
| description | Abstract Background Laryngeal cancer tends to have a very poor prognosis due to the unsatisfactory efficacy of chemotherapy for this cancer. Multidrug resistance (MDR) is the main cause of chemotherapy failure. The proto-oncogene c-fos has been shown to be involved in the development of MDR in several tumor types, but few studies have evaluated the relationship between c-fos and MDR in laryngeal cancer. We investigated the role of c-fos in MDR development in laryngeal cancer cells (cell line: human epithelial type 2, HEp-2) using the chemotherapeutic vincristine (VCR). Methods HEp-2/VCR drug resistance was established by selection against an increasing drug concentration gradient. The expressions of c-fos and multidrug resistance 1 (mdr1) were measured using qPCR and western blot. C-fos overexpression or knockdown was performed in various cells. The intracellular rhodamine-123 (Rh-123) accumulation assay was used to detect the transport capacity of P-glycoprotein (P-gp, which is encoded by the mdr1 gene). Results HEp-2 cells with VCR-induced resistance (HEp-2/VCR cells) were not only resistant to VCR but also evolved cross-resistance to other chemotherapeutic drugs. The expressions of the c-fos and mdr1genes were significantly higher in the HEp-2/VCR cells than in control cells. C-fos overexpression in HEp-2 cells (c-fos WT) resulted in increased P-gp expression and increased the IC50 for 5-FU. C-fos knockdown in the HEp-2/VCR cells (c-fos shRNA) resulted in decreased P-gp expression and decreased IC50 for 5-FU. An intracellular Rh-123 accumulation assay showed that the mean intracellular fluorescence intensity (MFI) was lower in the HEp-2/VCR cells than in HEp-2 cells. C-fos WT cells also showed lower MFI. By contrast, c-fos shRNA cells exhibited a higher MFI than the control group. Conclusion C-fos increased the expression of P-gp and mdr1 in the HEp-2/VCR cells, and enhanced the efflux function of the cells, thereby contributing to the development of MDR. |
| first_indexed | 2024-12-16T15:50:03Z |
| format | Article |
| id | doaj.art-3b007bdcd24341ef8907a4479b83743c |
| institution | Directory Open Access Journal |
| issn | 1425-8153 1689-1392 |
| language | English |
| last_indexed | 2024-12-16T15:50:03Z |
| publishDate | 2018-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cellular & Molecular Biology Letters |
| spelling | doaj.art-3b007bdcd24341ef8907a4479b83743c2022-12-21T22:25:43ZengBMCCellular & Molecular Biology Letters1425-81531689-13922018-02-0123111210.1186/s11658-017-0067-8C-fos upregulates P-glycoprotein, contributing to the development of multidrug resistance in HEp-2 laryngeal cancer cells with VCR-induced resistanceGuodong Li0Xiaoling Hu1Lu Sun2Xin Li3Jianfeng Li4Tongli Li5Xiaohui Zhang6Department of Otorhinolaryngology, Shanxi Provincial People’s Hospital Affiliated to Shanxi Medical UniversityDepartment of Pharmacology, Shanxi Medical UniversityDepartment of Otorhinolaryngology, Shanxi Provincial People’s Hospital Affiliated to Shanxi Medical UniversityDepartment of Otorhinolaryngology, Shanxi Provincial People’s Hospital Affiliated to Shanxi Medical UniversityDepartment of Otorhinolaryngology, Shanxi Provincial People’s Hospital Affiliated to Shanxi Medical UniversityDepartment of Otorhinolaryngology, Shanxi Provincial People’s Hospital Affiliated to Shanxi Medical UniversityArtificial Livers Treatment Center, Beijing YouAn Hospital, Capital Medical UniversityAbstract Background Laryngeal cancer tends to have a very poor prognosis due to the unsatisfactory efficacy of chemotherapy for this cancer. Multidrug resistance (MDR) is the main cause of chemotherapy failure. The proto-oncogene c-fos has been shown to be involved in the development of MDR in several tumor types, but few studies have evaluated the relationship between c-fos and MDR in laryngeal cancer. We investigated the role of c-fos in MDR development in laryngeal cancer cells (cell line: human epithelial type 2, HEp-2) using the chemotherapeutic vincristine (VCR). Methods HEp-2/VCR drug resistance was established by selection against an increasing drug concentration gradient. The expressions of c-fos and multidrug resistance 1 (mdr1) were measured using qPCR and western blot. C-fos overexpression or knockdown was performed in various cells. The intracellular rhodamine-123 (Rh-123) accumulation assay was used to detect the transport capacity of P-glycoprotein (P-gp, which is encoded by the mdr1 gene). Results HEp-2 cells with VCR-induced resistance (HEp-2/VCR cells) were not only resistant to VCR but also evolved cross-resistance to other chemotherapeutic drugs. The expressions of the c-fos and mdr1genes were significantly higher in the HEp-2/VCR cells than in control cells. C-fos overexpression in HEp-2 cells (c-fos WT) resulted in increased P-gp expression and increased the IC50 for 5-FU. C-fos knockdown in the HEp-2/VCR cells (c-fos shRNA) resulted in decreased P-gp expression and decreased IC50 for 5-FU. An intracellular Rh-123 accumulation assay showed that the mean intracellular fluorescence intensity (MFI) was lower in the HEp-2/VCR cells than in HEp-2 cells. C-fos WT cells also showed lower MFI. By contrast, c-fos shRNA cells exhibited a higher MFI than the control group. Conclusion C-fos increased the expression of P-gp and mdr1 in the HEp-2/VCR cells, and enhanced the efflux function of the cells, thereby contributing to the development of MDR.http://link.springer.com/article/10.1186/s11658-017-0067-8C-fosP-glycoproteinMultidrug resistanceLaryngeal carcinoma |
| spellingShingle | Guodong Li Xiaoling Hu Lu Sun Xin Li Jianfeng Li Tongli Li Xiaohui Zhang C-fos upregulates P-glycoprotein, contributing to the development of multidrug resistance in HEp-2 laryngeal cancer cells with VCR-induced resistance Cellular & Molecular Biology Letters C-fos P-glycoprotein Multidrug resistance Laryngeal carcinoma |
| title | C-fos upregulates P-glycoprotein, contributing to the development of multidrug resistance in HEp-2 laryngeal cancer cells with VCR-induced resistance |
| title_full | C-fos upregulates P-glycoprotein, contributing to the development of multidrug resistance in HEp-2 laryngeal cancer cells with VCR-induced resistance |
| title_fullStr | C-fos upregulates P-glycoprotein, contributing to the development of multidrug resistance in HEp-2 laryngeal cancer cells with VCR-induced resistance |
| title_full_unstemmed | C-fos upregulates P-glycoprotein, contributing to the development of multidrug resistance in HEp-2 laryngeal cancer cells with VCR-induced resistance |
| title_short | C-fos upregulates P-glycoprotein, contributing to the development of multidrug resistance in HEp-2 laryngeal cancer cells with VCR-induced resistance |
| title_sort | c fos upregulates p glycoprotein contributing to the development of multidrug resistance in hep 2 laryngeal cancer cells with vcr induced resistance |
| topic | C-fos P-glycoprotein Multidrug resistance Laryngeal carcinoma |
| url | http://link.springer.com/article/10.1186/s11658-017-0067-8 |
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