Thyroid hormone receptor β1 suppresses proliferation and migration by inhibiting PI3K/Akt signaling in human colorectal cancer cells

Zhu, Lei; Tian, Guang-Ang; Yang, Qin; De, Gejing; Zhang, Zhigang; Wang, Yahui; Nie, Hui; Yang, Xiaomei; Li, Jun

doi:10.3892/or.2016.4931

Cited by 26 publications

(23 citation statements)

References 28 publications

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“…The Akt signaling pathway principally regulates the activity of cancer cells (30,31). Previous studies have indicated that the Akt signaling pathway is a key factor in the viability and migration of a number of types of tumor including colorectal (32), and prostate cancer (33), and glioblastoma (34) and osteosarcoma (35). Additionally, the Akt signaling pathway is an important regulator of breast cancer (36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%

Tetramethylpyrazine regulates breast cancer cell viability, migration, invasion and apoptosis by affecting the activity of Akt and caspase-3

Shen¹,

Zeng²,

Pan³

et al. 2018

Oncol Lett

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Abstract. Tetramethylpyrazine (TMP), an effective component of the traditional Chinese medicine Chuanxiong Hort, has been proven to exhibit a beneficial effect in a number of types of malignant epithelial cancer. However, the mode of action of TMP on breast cancer cells remains unknown. The aim of the present study was to investigate the regulatory effect of TMP on breast cancer cells and its underlying molecular mechanism of action. Different concentrations of TMP were used to treat breast cancer cells, and subsequently, the effects on the viability, apoptosis, and migration and invasion abilities were determined. In addition, the expression and activity levels of the protein kinase B (Akt) signaling pathway and caspase-3 were explored via reverse transcription-quantitative polymerase chain reaction and western blot analysis. The results of the present study revealed that TMP significantly inhibited the viability, migration and invasion rates, and increased the apoptosis of MDA-MB-231 cells in a dose-dependent manner. The minimum effective dose was ~1,600 µM. Additional mechanistic studies demonstrated that 1,600 and 3,200 µM TMP significantly decreased the gene expression and activity of Akt and increased the activity of caspase-3. This mechanism may be responsible for the inhibition of viability, migration and invasion, and activation of apoptosis in breast cancer cells. The results of the present study suggested that TMP may be used in chemotherapy against breast cancer.

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Section: Discussionmentioning

confidence: 99%

Tetramethylpyrazine regulates breast cancer cell viability, migration, invasion and apoptosis by affecting the activity of Akt and caspase-3

Shen¹,

Zeng²,

Pan³

et al. 2018

Oncol Lett

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“…Because thyroxin affects important metabolic pathways such as AMPK (Adenosine 5’-monophosphate (AMP)-activated protein kinase) pathway and PI3K/Akt pathway, altered levels of metabolites in patients with hypothyroxemia have been the focus of many thyroid disease studies [14–16]. In recent years, metabolomic studies have provided the advanced methods necessary to identify changing metabolite levels, resulting in rapid progress in disease biomarker discovery [17–19].…”

Section: Introductionmentioning

confidence: 99%

Maternal low thyroxin levels are associated with adverse pregnancy outcomes in a Chinese population

Zhang

Dai

et al. 2017

PLoS ONE

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Although thyroid dysfunction in early pregnancy may have adverse effects on pregnancy outcomes, few studies have examined the relationship between maternal low free thyroxin (FT4) levels in both first and third trimesters of pregnancy and the incidence of adverse pregnancy outcomes. We hypothesized that low FT4 levels in either first or third trimesters of pregnancy may have different effects on pregnancy outcomes. The study included 6,031 mothers who provided both first and third pregnancy serum samples for analyses of thyroid function. Adverse pregnancy outcomes, such as gestational diabetes mellitus (GDM), pregnancy-induced hypertension and preeclampsia, were diagnosed using the oral glucose tolerance test, blood pressure and urine protein test. Serum metabolites like adenosine and its analogues were identified using hydrophilic interaction liquid chromatography (HILIC)-tandem mass spectrometry (MS/MS). The incidence of hypothyroidism in pregnant women tended to increase with age and pre-pregnancy body mass index (BMI). The incidence of GDM was negatively correlated with maternal FT4 levels during early pregnancy while the incidence of preeclampsia was negatively correlated with maternal FT4 levels during late pregnancy. The incidence of pregnancy-induced hypertension was not significantly correlated with maternal FT4 levels. The women who had isolated maternal hypothyroxemia (IMH) in the third trimester of pregnancy had an increased risk of developing preeclampsia. Some metabolites like adenosine and its analogues in the serum were significantly changed in pregnant mothers with IMH. In conclusion, low FT4 levels during pregnancy are a risk factor for GDM and preeclampsia. Adenosine and its analogues may be important bridges between IMH and preeclampsia.

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“…The abovementioned effects of m-TRβ1 were significantly stronger than those of TRβ1. Studies have shown that TRβ1 can inhibit the proliferation and migration of hepatocarcinoma cells and other cancer cells [ 2 , 4 , 6 , 15 , 23 – 25 ]. Cell apoptosis is a complicated biological process that is associated with complex signaling pathway responses.…”

Section: Discussionmentioning

confidence: 99%

“…TRs regulate target gene transcription by interacting with specific DNA sequences, known as thyroid hormone response elements (TREs) [ 3 ]. Several recent studies have strongly suggested that TRβ plays an important role in cell proliferation and malignant transformation [ 4 – 7 ]. Low or even no expression of TRs and alterations in TR genes, especially TRβ1, have been identified in many types of cancer [ 8 – 12 ].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of modified human TRβ1 suppresses the growth of hepatocarcinoma SK-hep1 cells in vitro and in xenograft models

et al. 2018

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Association studies suggest that TRβ1 functions as a tumor suppressor. Thyroid hormone receptors (TRs) mediate transcriptional responses through a highly conserved DNA-binding domain (DBD). We previously constructed an artificially modified human TRβ1 (m-TRβ1) via the introduction of a 108-bp exon sequence into the corresponding position of the wild-type human TRβ1 (TRβ1) DBD. Studies confirmed that m-TRβ1 was functional and could inhibit the proliferation of breast cancer MDA-MB-468 cells in vitro. To understand the role of m-TRβ1 in liver tumor development, we adopted a gain-of-function approach by stably expressing TRβ (m-TRβ1 and TRβ1) genes in a human hepatocarcinoma cell line, SK-hep1 (without endogenous TRβ), and then evaluated the effects of the expressed TRβ on cancer cell proliferation, migration, and tumor growth in cell-based studies and xenograft models. In the presence of 3,5,3-l-triiodothyronine (T3), the expression of TRβ in SK-hep1 cells inhibited cancer cell proliferation and impeded tumor cell migration through the up-regulation of 4-1BB, Caspase-3, and Bak gene expression; down-regulation of Bcl-2 gene expression; and activation of the Caspase-3 protein. TRβ expression in SK-hep1 led to less tumor growth in xenograft models. Additionally, the anti-tumor effect of m-TRβ1 was stronger than that of TRβ1. These data indicate that m-TRβ1 can act as a tumor suppressor in hepatocarcinoma and its role was significantly better than that of TRβ1.

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Thyroid hormone receptor β1 suppresses proliferation and migration by inhibiting PI3K/Akt signaling in human colorectal cancer cells

Cited by 26 publications

References 28 publications

Tetramethylpyrazine regulates breast cancer cell viability, migration, invasion and apoptosis by affecting the activity of Akt and caspase-3

Tetramethylpyrazine regulates breast cancer cell viability, migration, invasion and apoptosis by affecting the activity of Akt and caspase-3

Maternal low thyroxin levels are associated with adverse pregnancy outcomes in a Chinese population

Overexpression of modified human TRβ1 suppresses the growth of hepatocarcinoma SK-hep1 cells in vitro and in xenograft models

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