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

## TL;DR

This study shows that increasing SHP-1 in nasopharyngeal cancer cells makes them more resistant to radiation, less likely to age, and changes their cell cycle.

## Contribution

The study reveals SHP-1's role in radioresistance, senescence, and cell cycle redistribution in NPC cells.

## Key findings

- SHP-1 downregulation increases radiosensitivity and senescence in NPC cells.
- SHP-1 overexpression causes radioresistance and S-phase cell cycle arrest.
- SHP-1 affects cell cycle proteins like CDK4, cyclin D1, and p16 in NPC cells.

## Abstract

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.

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.

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).

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.