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01 February 2018 : Laboratory Research  

Shikonin Inhibites Migration and Invasion of Thyroid Cancer Cells by Downregulating DNMT1

Yue Zhang1ABCDEF, Bin Sun2ABCDE, Zhi Huang3BDE, Dai-Wei Zhao4AF, Qingfan Zeng5AFG*

DOI: 10.12659/MSM.908381

Med Sci Monit 2018; 24: LBR661-670

Abstract

BACKGROUND: Shikonin is a component of Chinese herbal medicine. The aim of this study was to investigate the effects of shikonin on cell migration of papillary thyroid cancer cells of the TPC-1 cell line in vitro and expression levels of the phosphate and tensin homolog deleted on chromosome 10 (PTEN) and DNA methyltransferase 1 (DNMT1) genes.

MATERIAL AND METHODS: The Cell Counting Kit-8 (CCK-8) assay was performed to evaluate the proliferation of TPC-1 papillary thyroid cancer cells, and the normal thyroid cells, HTori-3, in vitro. A transwell motility assay was used to analyze the migration of TPC-1 cells. Western blot was performed to determine the expression levels of PTEN and DNMT1 genes. A methylation-specific polymerase chain reaction (PCR) (MSP) assay was used to evaluate the methylation of PTEN.

RESULTS: Following treatment with shikonin, the cell survival rate of TPC-1 cells decreased in a dose-dependent manner; the inhibitory effects on HTori-3 cells were less marked. Shikonin inhibited TPC-1 cell migration and invasion in a dose-dependent manner. The methylation of PTEN was suppressed by shikonin, which also reduced the expression of DNMT1 in a dose-dependent manner, and increased the expression of PTEN. Overexpression of DNMT1 promoted the migration of TPC-1 cells and the methylation of PTEN. Levels of protein expression of PTEN in TPC-1 cells treated with shikonin decreased, and were increased by DNMT1 knockdown.

CONCLUSIONS: Shikonin suppressed the expression of DNMT1, reduced PTEN gene methylation, and increased PTEN protein expression, leading to the inhibition of TPC-1 cell migration.

Keywords: Methylation, PTEN Phosphohydrolase

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750