Simvastatin inhibits proliferation and promotes apoptosis of oral squamous cell carcinoma through KLF2 signal

  • J Oral Biosci. 2023 Aug 23;S1349-0079(23)00122-6. doi: 10.1016/j.job.2023.08.006.
Yuying Kou  1 ,  Yuan Zhang  1 ,  Xing Rong  1 ,  Panpan Yang  1 ,  Caijiao Wang  1 ,  Qin Zhou  1 ,  Hongrui Liu  1 ,  Bo Liu  2 ,  Minqi Li  3
Affiliations
  • 1. Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, China; Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China.
  • 2. School of Clinical Medicine, Jining Medical University, Jining, China; Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China. Electronic address: [email protected].
  • 3. Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, China; School of Clinical Medicine, Jining Medical University, Jining, China; Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China. Electronic address: [email protected].
PMID: 37625505 DOI: 10.1016/j.job.2023.08.006
Abstract

Objectives: This study aimed to explore the role and specific mechanism of the cholesterol-lowering drug simvastatin in inhibiting oral squamous cell carcinoma (OSCC).

Methods: The proliferation, Apoptosis, and migration levels of OSCC cells were detected by CCK8, quantitative real-time polymerase chain reaction, western blot, colony formation, TdT-mediated dUTP Nick-End Labeling assay, and wound healing assay. The inhibitory effect of simvastatin in vivo was detected by a mouse xenograft tumor model. Immunohistochemistry and immunofluorescence staining were used to assess the KLF2 and β-catenin expressions in cells and tissues.

Results: KLF2 expression in OSCC cells and tissues was downregulated. The addition of KLF2 inducer, GGTI298, inhibited the proliferation and migration of OSCC cells. Simvastatin played a role in inhibiting the proliferation and promoting the Apoptosis of OSCC cells. Moreover, it inhibited β-catenin expression and promoted KLF2 expression in OSCC cells. KLF2 siRNA reversed the effect of simvastatin on the proliferation and Apoptosis of OSCC cells.

Conclusions: KLF2, as a tumor suppressor gene, may be an important marker for diagnosing and treating OSCC. Simvastatin inhibits the progression of OSCC by regulating the KLF2 signal.

Keywords
Krüppel like factor 2; Simvastatin; apoptosis; oral squamous cell carcinoma; proliferation; β-catenin.
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