Abstract

Prunella vulgaris, a traditional Chinese medicine, has been used to treat various benign and malignant tumours for centuries in China. In our previous studies, Prunella vulgaris extract (PVE) was shown to promote apoptosis in differentiated thyroid cancer (DTC) cells. However, whether other mechanisms are involved in the antitumour effect of PVE in thyroid cancer (TC) cells remains unclear. The present study aimed to investigate the antiproliferative and antimigratory effects of PVE on TC cell lines both in vitro and in vivo. First, the TPC-1 and SW579 human TC cell lines were screened by MTT assay for their high level of sensitivity to PVE. Then, the results of cell growth curve and colony formation assay and cell cycle analyses, wound healing, and migration assays demonstrated that PVE inhibited the proliferation and migration of TPC-1 and SW579 cells. Moreover, the antitumour effect of PVE was verified in a subcutaneous xenotransplanted tumour model. Next, MKI67, PCNA, CTNNB1, and CDH1 were screened by qRT-PCR for their significantly differential expression levels in xenograft tissue with and without PVE treatment, and expression of MKI67, PCNA, and CDH1 was verified by Western blot. Finally, an integrated bioinformatics analysis containing protein-protein interaction network, KEGG pathway, and GO analysis was conducted to explore more potential antitumour mechanisms of PVE. In summary, PVE could inhibit the proliferation and migration of TC cells both in vitro and in vivo, which may have been achieved by modulation of the expression of MKI67, PCNA, and CDH1. These data suggest that PVE has the potential to be developed into a new anticancer drug for the treatment of TC.

Highlights

  • Cancer of the thyroid gland is the most common endocrine malignancy that has rapidly increased in global incidence in recent years [1]

  • Among the four human TC cell lines examined, the TPC-1 papillary thyroid cancer cell line and the SW579 squamous thyroid cancer cell line were selected for our subsequent experiments due to their high sensitivity to Prunella vulgaris extract (PVE). e half maximal inhibitory concentration (IC50) values calculated from the inhibition ratios of PVE against TPC-1 and SW579 cells (Table S1: Inhibitory effect of PVE at different concentrations on TPC-1 and SW579 cells at 48 h) were 9.294 mg/mL and 6.669 mg/mL, respectively

  • PVE solutions used in our subsequent in vitro experiments were selected according to the corresponding IC50 value

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Summary

Introduction

Cancer of the thyroid gland is the most common endocrine malignancy that has rapidly increased in global incidence in recent years [1]. Surgical resection, iodine-131 radiotherapy, and long-term thyroid-stimulating hormone (TSH) suppression remain the three major treatments for DTC [3]. Erefore, finding an alternative or adjuvant therapy, such as some herbal and botanical remedies used in oncotherapy, may be of great importance. Surgery might result in various complications, such as hypocalcemia, hoarseness, or postoperative bleeding [4], while iodine-131 treatment and TSH inhibitory therapy have limited efficacy and can cause a series of adverse reactions [5, 6]. Due to their limited side effects and low toxicity, herbal medicines are widely used in China and the United States, where over one-quarter of adults have tried such remedies within the past few years [7]. More than a thousand years ago, Prunella vulgaris extract (PVE) had been

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