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01.12.2018 | Primary research | Ausgabe 1/2018 Open Access

Cancer Cell International 1/2018

Conserved cell populations in doxorubicin-resistant human nasal natural killer/T cell lymphoma cell line: super multidrug resistant cells?

Zeitschrift:
Cancer Cell International > Ausgabe 1/2018
Autoren:
Xudong Zhang, Xiaorui Fu, Meng Dong, Zhenzhen Yang, Shaoxuan Wu, Mijing Ma, Zhaoming Li, Xinhua Wang, Ling Li, Xin Li, Zhenchang Sun, Yu Chang, Feifei Nan, Jiaqin Yan, Yun Mao, Mingzhi Zhang, Qingjiang Chen

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.
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