RESUMEN
This study determined the chemosensitizing potential of ginsenoside Rg1 in triple-negative MDA-MB-231 breast cancer cell lines. Ginsenoside Rg1 (10 µM) treated breast cancer cells were exposed to 8 nM of doxorubicin, and the chemosensitizing potential was measured by cell-based assays. Ginsenoside Rg1 (10 µM) treatment lowered the doxorubicin IC50 value to 0.01 nM. Furthermore, the ginsenoside pretreatment augments doxorubicin-mediated reactive oxygen species (ROS) generation and subsequent alterations of mitochondrial membrane potential in MDA-MB-231 cell lines. The alkaline comet assay results illustrated an increased % tail DNA during ginsenoside Rg1 plus doxorubicin treatment than doxorubicin alone treatment. In addition, the number of apoptotic cells was also increased in ginsenoside Rg1 plus doxorubicin-treated cells. Furthermore, the polymerase chain reaction array results illustrate activation of mitogen-activated protein kinase (MAPK) gene expression (AKT, ERK, and MAPK) during doxorubicin alone treatment and it has been attenuated by ginsenoside Rg1 pretreatment. Moreover, ginsenoside Rg1 treatment before doxorubicin activates the DNA damage response elements (ATM, H2AX, RAD51, and XRCC1) and subsequent apoptosis-related gene expression (p21, TP53. APAF1, Bax, CASP3, and CASP9) patterns in MDA-MB-231 cell lines. The ginsenoside Rg1 plus doxorubicin combination shows less cytotoxicity and ROS generation in MDA10A normal breast cancer cell lines. Therefore, the present results support the chemosensitizing property of ginsenoside Rg1 in triple-negative breast cancer cell lines.
Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias de la Mama , Doxorrubicina/farmacología , Ginsenósidos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Femenino , HumanosRESUMEN
INTRODUCTION: Hepatocellular carcinoma (HCC) remains one of the most predominant types of digestive system malignancies worldwide. TNF-related apoptosis-inducing ligand (TRAIL) is a biological cytokine with the mentioned specificity, but some tumor cells' resistance limits its use as a therapeutic approach. The present study aimed to investigate thymoquinone (TQ) and TRAIL's combined effect and the potential mechanisms in human hepatic HepG2 carcinoma cells. METHODS: Cell viability and IC50 dose for TQ and TRAIL, alone and in combination, were determined using the MTT method. ELISA evaluated the expression levels of 8-Hydroxy-2'-deoxyguanosine. The apoptosis rate was assessed by flow cytometry, ELISA cell death assay, and caspase 8 activity assays. The mRNA and protein evaluation of candidate genes, including survivin, Bcl-2, XIAP, c-IAP1, c-IAP2, and c-FLIP, were accomplished before and after the treatment using qRT-PCR and Western blot analysis, respectively. RESULTS: Our results showed that TQ synergistically increased TRAIL's cell toxic effects as follows: TQ plus TRAIL > TRAIL > TQ. TQ could sensitize the HepG2 cells against the TRAIL-induced apoptosis and amplify the caspase 8 activity. This outcome is achieved by decreasing the mRNA and protein expression levels of anti-apoptotic genes. CONCLUSIONS: Our findings suggest that TQ can sensitize the human HCC cell line HepG2 against TRAIL by inducing the death receptor pathway. Moreover, these agents' combinational therapy might promise a therapeutic regimen for improving the clinical efficacy of TRAIL-induced apoptosis in patients with HCC.
Asunto(s)
Apoptosis , Benzoquinonas/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Daño del ADN , Neoplasias Hepáticas/tratamiento farmacológico , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Benzoquinonas/uso terapéutico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/fisiopatología , ADN/efectos de los fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/fisiopatología , Estrés OxidativoRESUMEN
OBJECTIVE: To study the effect of matrine on tumor growth, inflammatory factors and immune function in Wistar rat with breast cancer. METHODS: Sixty female Wistar rats were randomly divided into control group (n=10) and the modeling group of breast cancer cell tumor-bearing rat (n=50), then the rats in modeling group were randomly divided into five groups (n=10):vehicle group, matrine low dose group (50 mg/kg), medium dose group (100 mg/kg), high dose group (200 mg/kg), and lentinan group (200 mg/kg). Except the control group, each rat in the other groups was subcutaneously inoculated 0.4 ml Walker 256 breast cancer cell suspension (5×107 cells/ml) in the right axillary. Each group was treated with corresponding drug by ig administration (10 ml/kg body weight) twice a day for 14 days. After 14 days, the blood sample was collected from ventral aorta, the tumor was removed and weighed to calculate tumor inhibitory rate. The levels of interleukin-2 (IL-2), interferon-γ (IFN-γ), interleukin-6 (IL-6), interleukin-10 (IL-10), transforming growth factor-ß (TGF-ß), CD3+, CD4+, CD8+, IgG, IgM, IgA in peripheral blood were determined. RESULTS: The mean tumor weight of matrine low-dose, medium-dose, high-dose groups and lentinan group were (4.99±0.93) g, (4.52±0.92) g, (4.22±1.18) g and (4.52±0.92) g respectively, which were significantly lower than that in model group. There was no statistical difference on the mean tumor weight among matrine groups and lentinan group (P>0.05). After the drug intervention, the tumor inhibitory rates of matrine low-dose, medium dose, high-dose groups and lentinan group were 24.6%, 31.7%, 36.3%, and 27.9% respectively, there was no statistical difference among the four groups. The levels of IL-2, IFN-γ, CD8+ in vehicle group were lower than those of control group obviously (P<0.01), however, the levels of IL-6, IL-10, TGF-ß, CD3+, CD4+, IgG, IgM, IgA were higher significantly than those of control group (P<0.01). The levels of IL-2, IFN-γ, CD8+ in matrine low-dose, medium dose, high-dose groups and lentinan group were higher than those of vehicle group obviously (P<0.01, P<0.05); while the levels of IL-6, IL-10, TGF-ß, CD3+, CD4+, IgG, IgM, IgA were lower than those of model group markedly (P<0.01, P<0.05). The levels of IgM and IgA in matrine low-dose and medium-dose groups were higher than those of lentinan group obviously (P<0.01, P<0.05); the levels of IL-2, IFN-γ and IgA in matrine high-dose group were higher than those of lentinan group obviously (P<0.01, P<0.05); while the levels of IFN-γ in matrine low-dose group were lower than those of lentinan group markedly (P<0.05); the levels of IL-10 and CD4+ in matrine high-dose group were lower than those of lentinan group markedly (P<0.01, P<0.05). CONCLUSIONS: Matrine has an obvious antitumor action which is related to its ability to enhance cellular and humoral immunity, reduce inflammatory reaction.