West China Journal of Stomatology ›› 2022, Vol. 40 ›› Issue (3): 320-327.doi: 10.7518/hxkq.2022.03.012

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Effect of protein kinase D inhibitor CRT0066101 on the cell migration of salivary adenoid cystic carcinoma

Chen Jiao(), Die Lü, Chen Hongli, Zhang Ping.()   

  1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2021-06-02 Revised:2022-04-10 Online:2022-06-01 Published:2022-06-01
  • Contact: Zhang Ping. E-mail:cj0123@163.com;pingzhang68@hotmail.com
  • Supported by:
    The National Natural Science Foundation of China(81802717);The Sichuan Science and Technology Project(2020YJ0290);Correspondence: Zhang Ping, E-mail: pingzhang68@hotmail.com

Abstract: Objective

This study aimed to study the effect of the protein kinase D (PKD) inhibitor CRT0066101 on the cell migration of salivary adenoid cystic carcinoma (SACC) cells in vitro and explore its related mechanisms to provide new strategies into the clinical treatment of SACC cells.

Methods

SACC-LM cells were treated with different concentrations of CRT0066101, and the effect of active phospho-PKD was detected through Western blot and cell immunofluorescence staining. Transwell assay was performed to test cell migration. The effect of CRT0066101 on the protein expression related to the epithelial mesenchymal transition (EMT) was detected through Western blot, cell immunofluorescence staining, and quantitative real-time polymerase chain reaction (qRT-PCR). The cells were treated with the proteasome inhibitor after CRT0066101 administration, and the expression of Snail protein was detected by Western blot.

Results

CRT0066101 inhibited PKD activity and reduced the number of invaded cells in SACC-LM cells. CRT0066101 decreased the expression of N-cadherin and Snail and increased the expression of E-cadherin in SACC-LM cells. The regulation of snail protein degradation by CRT0066101 was dependent on the proteasome pathway.

Conclusion

CRT0066101 can inhibit the migration of SACC-LM cells in SACC and regulate the expression of proteins and genes related to EMT. The mechanism may be associated with the proteasome-dependent degradation of Snail.

Key words: salivary adenoid cystic carcinoma, CRT0066101, cell migration, epithelial mesenchymal transition

CLC Number: