Abstract
BackgroundRadioresistance 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.MethodsSHP-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.ResultsCompared 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).ConclusionSHP-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.
Highlights
Radioresistance is the main limit to the efficacy of radiotherapy in nasopharyngeal carcinoma (NPC)
Real-time RT-PCR showed that SHP-1 mRNA expression was suppressed by 62.5 % in CNE-1 cells transduced with lentivirus-mediated SHP-1 shRNA (CNE-1 SHP-1 shRNA), compared with cells transduced with lentivirus-mediated scramble shRNA (CNE-1-scramble shRNA), while SHP-1 mRNA expression was overexpressed 249.2 folds in CNE-2 cells transduced with lentivirus-mediated SHP-1 overexpression (CNE-2 SHP-1 overexpression), compared with cells transduced with lentivirus vector (CNE-2-empty vector) (Fig. 1e)
Results showed that SHP-1 downregulation resulted in increased senescence, increased radiosensitivity, higher proportion of cells in G0/G1, decreased expression of CDK4, cyclin D1, cyclin E, Rb, and pRb, and increased expression of p16
Summary
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. Nasopharyngeal carcinoma (NPC) is a cancer with a distinctly skewed geographic and ethnic distribution, and is endemic in Southern China and South East Asia [1]. Tobacco and alcohol are the two main risk factors for NPC [2,3,4]. Human papillomavirus and Epstein-Barr virus increase the risk of NPC, in endemic regions [5, 6]. Mean survival of patients with stage I, II, or III NPC is about 3 years [7]
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