Journal
RADIATION ONCOLOGY
Volume 10, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s13014-015-0445-1
Keywords
Nasopharyngeal carcinoma; SHP-1; Cellular senescence; Cell cycle distribution; p16; Rb
Funding
- Natural Sciences Foundation of China [81301976]
- Wu Jieping Medical Foundation
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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 beta-galactosidase assay was used to assess senescence. Western blot was used to assess SHP-1, p21, p53, pRb, Rb, H3K9Me3, HP1 gamma, 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.
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