Hypoxia increases chemotherapy resistance in nasopharyngeal carcinoma via inducing CDK6 deSUMOylation
10.3760/cma.j.issn.1673-0860.2019.07.008
- VernacularTitle: 乏氧诱导CDK6与SUMO1解离对鼻咽癌化疗抵抗的作用
- Author:
Qing REN
1
;
Fengting LIU
2
;
Chunyan ZHANG
3
;
Lili LI
4
;
Ruizhen CHENG
3
;
Xiaozhi LIU
5
;
Qiang LIU
6
;
Huifang ZHOU
7
Author Information
1. Department of Otorhniolaryngology, the Fifth Central Hospital of Tianjin, Tianjin 300450, China
2. Clinical Medical College of Tianjin Medical University, Tianjin 300070, China
3. Department of Pharmacy, Tianjin Binhai New Area Hospital of Traditional Chinese Medicine, Tianjin 300450, China
4. Department of Bone and Soft Tissue Oncology, Tianjin Medical University Cancer Hospital, Tianjin 300060, China
5. Central Laboratory, the Fifth Central Hospital of Tianjin, Tianjin 300450, China
6. Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China
7. Department of Otorhinolaryngology, Tianjin Medical University General Hospital, Tianjin 300070, China
- Publication Type:Journal Article
- Keywords:
Nasopharyngeal neoplasms;
Small ubiquitin-related modifier proteins;
Cyclin-dependent kinase 6;
Anoxia;
Chemotherapy resistance
- From:
Chinese Journal of Otorhinolaryngology Head and Neck Surgery
2019;54(7):524-528
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To understand the mechanism of chemotherapy resistance in nasopharyngeal carcinoma under hypoxic conditions through the perspective of protein SUMOylation modification.
Methods:Cobalt chloride (CoCl2) was used to establish the hypoxic model of human nasopharyngeal carcinoma CNE1 cells. Then, the cell cycle was detected by flow cytometry, and the expression level of small ubiquitin-related modifier(SUMO) and cyclin-dependent kinase 6 (CDK6) proteins were detected by western blotting. MTT assay was used to determine the median lethal dose (IC50) of cancer cells against cisplatin, and enzyme-linked immunosorbent assay (ELISA) was used to determine lactate dehydrogenase (LDH) level.
Results:The cell cycle of CNE1 induced by hypoxia was arrested in G0/G1 phase.The results of Western blot showed that the protein expression level of CDK6 in CNE1 cells was lower than that in the control group (0.83±0.25 vs. 0.43±0.21, t=14.67, P=0.003). The protein level of conjugated SUMO1 was significantly lower than that in the control group (2.69±0.48 vs. 1.38±0.31, t=17.22, P=0.001), while the level of free SUMO1 protein was significantly higher than that in the control group (2.01±0.43 vs. 2.60±0.59, t=15.45, P=0.002).The LC50 of CNE1 cells in the control group was significantly lower than that in the hypoxic group (29.44 μg/ml vs. 97.72 μg/ml, t=12.79, P=0.001). After CNE1 cells received 50 μg/ml cisplatin for 48 h, the LDH content in the supernatant of the control group was significantly higher than that in the hypoxic group ((541.49±64.59) ng/ml vs. (234.67±41.03) ng/ml, t=11.94, P=0.007)). The apoptosis rate of CNE1 cells in the control group was significantly higher than that in the hypoxic group ((76.64±5.37)% vs. (32.84±4.77) ng/ml, t=8.49, P=0.003)).
Conclusion:Hypoxia can dissociate the covalent modification of CDK6 and SUMO1, inhibit cell cycle and increase the chemotherapy resistance of nasopharyngeal carcinoma.
