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- Title
Conserved cell populations in doxorubicin-resistant human nasal natural killer/T cell lymphoma cell line: super multidrug resistant cells?.
- Authors
Zhang, Xudong; Fu, Xiaorui; Dong, Meng; Yang, Zhenzhen; Wu, Shaoxuan; Ma, Mijing; Li, Zhaoming; Wang, Xinhua; Li, Ling; Li, Xin; Sun, Zhenchang; Chang, Yu; Nan, Feifei; Yan, Jiaqin; Mao, Yun; Zhang, Mingzhi; Chen, Qingjiang
- Abstract
Background: Extranodal NK/T-cell lymphoma, nasal type (ENKL) is a distinct clinicopathological entity and EBV-associated disease that is highly aggressive. Many patients had failed to respond to conventional chemotherapy or relapsed after treatment. Multi-drug resistance is a major cause that leads to these desperate failures. However, the specific mechanism of drug resistance is still unclear. Methods: In the previous study, we firstly developed a doxorubicin-resistant ENKL cell line known as SNK-6/ADM, and then a small quantity of side population (SP) cells were derived from SNK-6/ADM and named SNK-6/ADM-SP. In order to explore the biological characteristics and mechanism of drug-resistance of these cells, SNK-6, SNK-6/ADM and SNK-6/ADM-SP cells were utilized to evaluate potentially differences of chemotherapy resistance index (RI), morphology, proliferation, cell cycles, expression of ATP-binding cassette (ABC) transporters (ABCG1, ABCG2 and ABCC4) and surface markers, cytokine sensitivity, and situation of EBV infection. Results: We identified SNK-6/ADM-SP is a specific multidrug resistant cell population with a higher level of RI than SNK-6/ADM. Relevant evaluations showed that SNK-6/ADM-SP presented a series of conserved biological behaviors including relatively poor proliferation ability, high expression of ABCG2, weak sensitivity to IL-15 which could stimulate normal ENKL cells' proliferation and differentiation, and EBV inhibition with low level of EBV-DNA replication and EBV-antigen expression. Conclusions: This discovered cellular heterogeneity of ENKL could provide a new perspective to better understand the mechanisms of drug resistance and overcome elusive response to chemotherapy of ENKL.
- Subjects
T cells; LYMPHOMAS; MULTIDRUG resistance; CYTOKINES; CANCER chemotherapy
- Publication
Cancer Cell International, 2018, Vol 18, Issue 1, pN.PAG
- ISSN
1475-2867
- Publication type
Article
- DOI
10.1186/s12935-018-0644-6