1. Academic Validation
  2. Simvastatin inhibits proliferation and promotes apoptosis of oral squamous cell carcinoma through KLF2 signal

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

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: liubo7230@163.com.
  • 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: liminqi@sdu.edu.cn.
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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