Increased SHP-1 expression results in radioresistance, inhibition of cellular senescence, and cell cycle redistribution in nasopharyngeal carcinoma cells

Radiation Oncology

Gang Peng²  Gang Wu²  Qian Ding²  Zhenwei Zou²  Xiaofen Pan¹  Ziyi Sun² 

[1] Cancer center, Affliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong Province, China;Cancer Center, Union hosipital, Wuhan 430022, Hubei Province, China

关键词: Rb;    p16;    Cell cycle distribution;    Cellular senescence;    SHP-1;    Nasopharyngeal carcinoma;   

Others  :  1228493
DOI  :  10.1186/s13014-015-0445-1

 received in 2015-03-02, accepted in 2015-06-23,  发布年份 2015

【 摘 要 】

Background

Radioresistance is the main limit to the efficacy of radiotherapy in nasopharyngeal carcinoma (NPC). SHP-1 is involved in cancer progression, but its role in radioresistance and senescence of NPC is not well understood. This study aimed to assess the role of SHP-1 in the radioresistance and senescence of NPC cells.

Methods

SHP-1 was knocked-down and overexpressed in CNE-1 and CNE-2 cells using lentiviruses. Cells were irradiated to observe their radiosensitivity by colony forming assay. BrdU incorporation assay and flow cytometry were used to monitor cell cycle. A β-galactosidase assay was used to assess senescence. Western blot was used to assess SHP-1, p21, p53, pRb, Rb, H3K9Me3, HP1γ, CDK4, cyclin D1, cyclin E, and p16 protein expressions.

Results

Compared with CNE-1-scramble shRNA cells, SHP-1 downregulation resulted in increased senescence (+107 %, P < 0.001), increased radiosensitivity, higher proportion of cells in G0/G1 (+33 %, P < 0.001), decreased expressions of CDK4 (−44 %, P < 0.001), cyclin D1 (−41 %, P = 0.001), cyclin E (−97 %, P < 0.001), Rb (−79 %, P < 0.001), and pRb (−76 %, P = 0.001), and increased expression of p16 (+120 %, P = 0.02). Furthermore, SHP-1 overexpression resulted in radioresistance, inhibition of cellular senescence, and cell cycle arrest in the S phase. Levels of p53 and p21 were unchanged in both cell lines (all P > 0.05).

Conclusion

SHP-1 has a critical role in radioresistance, cell cycle progression, and senescence of NPC cells. Down-regulating SHP-1 may be a promising therapeutic approach for treating patients with NPC.

【 授权许可】

   
2015 Sun et al.

【 图 表 】

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