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Drug Des Devel Ther ; 15: 3697-3708, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34465981


Purpose: Puerarin (PR), a Chinese medicine rich in natural components, has been reported to display anti-fibrotic, antioxidant, anti-inflammatory and immunomodulatory properties. However, the protective mechanism of PR against unilateral ureteral obstruction (UUO)-mediated renal injury is not fully clarified. Therefore, the aim of this study was to investigate the effects of PR on UUO mice and its possible mechanisms. Methods: A total of 32 C57BL/6 mice were divided randomly into four groups (n=8): i) sham-operated group (Sham); ii) UUO group (UUO); iii) UUO + PR 50 mg/kg/day (UUO + PRL); and iv) UUO + PR 100 mg/kg/day (UUO + PRH). Continuous gavage administration for 14 days starting one week postoperatively, while the mice in Sham and UUO groups were given equal amounts of vehicle by the same means. All mice were then sacrificed and serum, 24-hour urine and tissue specimens were collected for renal function, histopathology, Western blot, immunohistochemistry. Results: Renal function and histopathology revealed that PR improved UUO-mediated renal dysfunction and partially reversed tubular injury and tubulointerstitial fibrosis. Additionally, according to the results of Western blot and immunohistochemistry, PR inhibited the expression of inflammatory factors including IL-1ß, IL-6, MCP-1 and ECM-related proteins including α-SMA, COL I and VIM. More importantly, the expression of fibrotic pathways TGF-ß1, Smad3, p-Smad3 and inflammatory pathways NF-κB p65, NF-κB p-p65, STAT3, p-STAT3 were inhibited to various extents under the PR treatment, while Smad7 was upregulated. Conclusion: These findings indicate that PR may inhibit the recruitment of inflammatory factors and extracellular matrix (ECM) deposition through the regulation of the NF-κB p65/STAT3 and TGFß1/Smads pathways, which alleviates the UUO-induced inflammatory and fibrotic response, thereby reversing renal injury.

J BUON ; 24(5): 1824-1829, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31786843


PURPOSE: Colon cancer ranks as the fourth common type of cancer and is responsible for significant morbidity and mortality throughout the world. Late diagnosis and the rarity of potent and safer chemotherapeutic drugs and efficient therapeutic targets create severe obstacle in the treatment of colon cancer. This study was undertaken to examine the anticancer effects of Evodiamine against human colon cancer cells. METHODS: The proliferation rate of the SW480 colon cancer cells was monitored by MTT assay. Apoptosis was detected by Annexin V/propidium iodide (PI) and acridine orange (AO)/ethidium bromide (EB) staining. Transmission electron microscopy (TEM) was used for detection of autophagy. Cell migration and invasion was detected by wound healing and transwell assays, respectively. Protein expression was determined by western blotting. RESULTS: Evodiamine suppressed the proliferation of the SW480 colon cancer cells and exhibited an IC50 of 10 µM. The cytotoxic effects of Evodiamine were found to be comparatively lower against the normal CDD-18Co colon cells as evidenced from the IC50 of 100 µM. AO/EB staining showed that Evodiamine caused apoptosis of the SW480 cells and the percentage of the apoptotic SW480 cells increased with increase in the Evodiamine concentration as indicated by annexin V/PI staining. Evodiamine-induced apoptosis was also accompanied by upregulation of caspase-3 and Bax and suppression of Bcl-2. TEM analysis showed that Evodiamine also activated autophagy in the SW480 cells by enhancing the expression of LC3 II and Beclin 1. The wound assay showed that Evodiamine suppressed the migration of the SW480 cells. Evodiamine also reduced the invasion potential of the SW480 cells as suggested by the transwell assay. CONCLUSION: The findings of the present study suggest that Evodiamine is a potent anticancer agent and may prove beneficial in the development of systemic therapy of colon cancer.

Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Quinazolinas/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Relacionadas à Autofagia/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/ultraestrutura , Humanos , Invasividade Neoplásica , Transdução de Sinais
Int J Mol Med ; 44(3): 1015-1025, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31257479


Breast cancer (BRCA) is the most common type of cancer in adult females. Estrogen receptor (ER)+/progesterone receptor (PR)+, human epidermal­growth factor receptor 2 (HER2)­ BRCA and triple­negative breast cancer (TNBC) are two important subtypes of this disease. Long non­coding RNA (lncRNA)­mediated transcriptional dysregulation triplets (lncTDTs) may contribute to the development of cancer; however, the precise functional roles of lncTDTs in ER+/PR+, HER2­ BRCA and TNBC require further investigation. In the present study, an integrated and computational approach was conducted to identify lncTDTs based on transcription factor (TF), gene, lncRNA expression profiles and experimentally verified TF­gene interactions. The regulatory patterns of these lncTDTs are complex and differed in ER+/PR+, HER2­ BRCA and TNBC. Of note, five common lncTDTs were reported for these BRCA subtypes. Functional analysis revealed lncTDTs to be enriched in the PI3K/AKT signaling pathway within the two BRCA subtypes. Additionally, certain lncTDTs were associated with survival and may be considered candidate prognostic biomarkers for BRCA subtypes. Collectively, the results of the present study provide novel insight into the functions and mechanisms of lncRNAs in ER+/PR+, HER2­ BRCA and TNBC, and may aid the development of targeted treatments against certain subtypes of BRCA.

Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Interferência de RNA , RNA Longo não Codificante/genética , Neoplasias de Mama Triplo Negativas/genética , Proteína BRCA2/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Modelos Biológicos , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Transcriptoma , Ubiquitina-Proteína Ligases/genética
Biomed Pharmacother ; 109: 1062-1069, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30551356


OBJECTIVE: Breast cancer is one of the most common malignant tumors in women with high mortality. Recent evidences have demonstrated that Ailanthone (AIL) could effectively inhibit tumor growth. However, whether AIL exerts anti-tumor effect on breast cancer remains unclear. The study aimed to investigate the effect of AIL on cell proliferation, apoptosis, migration and invasion in MDA-MB-231 cells. METHODS: After treatment with different concentrations (0-25 µM) of AIL, cell viability was detected by CCK-8 assay, and 10 µM AIL was noted as the optimum concentration for the following experiments. Then, cell proliferation, apoptosis, migration, invasion and relative protein levels were examined by BrdU, flow cytometry, Transwell assays, and western blot, respectively. The expression vectors of miR-148a mimic, miR-148a inhibitor were transfected into MDA-MB-231 cells, and the above experiments were determined again. The signal pathways of AMPK and Wnt/ß-catenin were finally analyzed by western blot assay. RESULTS: Cell viability was significantly decreased by AIL in a dose-dependent way. Moreover, AIL reduced the proliferation rate, and modulated CyclinD1, p53 and p21 expressions. AIL remarkably induced cell apoptosis with an increase in cleaved-Caspase-3/-9 expressions. Further, cell migration and invasion were decreased after treatment of AIL in MDA-MB-231 cells. AIL significantly up-regulated miR-148a expression. The effect of AIL on MDA-MB-231 cells was significantly enhanced by miR-148a overexpression, but reversed by miR-148a inhibition. Besides, we found that AIL blocked AMPK and Wnt/ß-catenin signal pathways by regulating miR-148a. CONCLUSIONS: These data demonstrated that AIL inhibited proliferation, migration and invasion of MDA-MB-231 cells by regulating miR-148a.

Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , MicroRNAs/genética , Quassinas/farmacologia , Regulação para Cima/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Invasividade Neoplásica/patologia , Transdução de Sinais/efeitos dos fármacos , Ativação Transcricional/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismo
J BUON ; 23(2): 340-345, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29745074


PURPOSE: Boswellic acid is an important plant-derived natural product with tremendous pharmacological potential and has been reported to inhibit the growth of several types of cancer cells. In this study we report the anticancer activity of boswellic acid against human colon cancer cells via induction of apoptosis, cell cycle arrest and inhibition of cell migration and PI3K/AKT signalling pathway. METHODS: The antiproliferative effects of boswellic acid were assessed by MTT assay using different doses of the drug. The apoptotic effects were studied by DAPI and annexin V/PI staining assays, and cell cycle distribution was studied by flow cytometry. The effects of the drug on PI3K/AKT protein expression were studied using western blot analysis. RESULTS: The results of this study showed that boswellic acid suppresses the growth of HCT-116 colon cancer cells. The anticancer effects were found to be dose-dependent and the IC50 value was 15 µM against the HCT-116 colon cancer cells. The inhibition of growth of these cancer cells was mainly due to apoptosis and G2/M cell cycle arrest. Besides, boswellic acid altered the Bax/Bcl-2 ratio in the HCT-116 cancer cells and inhibited their migration as indicated by the cell migration assay. It was observed that boswellic acid decreased the expression of p-PI3K and p-AKT in a concentration- dependent manner. However, the expression of PI3K and AKT remained almost unaltered. CONCLUSION: In conclusion, these results clearly suggest that boswellic acid could be employed in the treatment of colon cancer provided further in vivo and other in depth experiments are done.

Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Triterpenos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Células HCT116 , Humanos , Proteína Oncogênica v-akt/genética , Fosfatidilinositol 3-Quinases/genética , Transdução de Sinais/efeitos dos fármacos
Oncol Res ; 25(8): 1363-1371, 2017 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-28247844


miR-152, as a tumor suppressor, has been reported to be downregulated in a number of cancer cell lines and tumor tissues, including breast cancer. This study aimed to investigate the role of miR-152 in human breast cancer and its underlying mechanisms. Human breast cancer cell line HCC1806 was transfected with hsa-miR-152-3p mimic, inhibitor, or scrambled negative controls. The efficiency of miR-152-3p transfection was evaluated by quantitative real-time PCR, and the effects on cell viability and apoptosis as well as on the PI3K/AKT signaling pathway were investigated by MTT assay, flow cytometry, and Western blot analysis, respectively. The binding effect of miR-152-3p on PIK3CA 3'-UTR was also investigated. The results suggested that miR-152-3p mimic transfection inhibited cell viability while inducing apoptosis of HCC1806 cells. Furthermore, miR-152-3p negatively regulated PIK3CA expression via binding to the 3'-UTR of PIK3CA and decreased the phosphorylation levels of AKT (Ser473) and RPS6 (Ser235/236) in HCC1806 cells. miR-152-3p inhibitor transfection showed the opposite effects. In conclusion, miR-152-3p might serve as a tumor suppressor in human breast cancer cells via negatively regulating PIK3CA expression to inhibit the activation of AKT and RPS6, leading to suppression of HCC1806 cell proliferation.

Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Genes Supressores de Tumor , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Apoptose/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Feminino , Técnicas de Silenciamento de Genes , Humanos , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Transfecção