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Background and purpose:Breast cancer has the highest morbidity and mortality rate in women worldwide. Triple-negative breast cancer (TNBC) has no speciifc target and has low survival rate. Recent studies have veriifed BRD4 could promote tumor progression. This study aimed to detect the expression level of BRD4 in TNBC after treatment with gemcitabine, and to reveal the effect ofBRD4 silencing plus gemcitabine as a treatment for TNBC. Methods:The expression ofBRD4 in TNBC cell lines treated with gemcitabine was detected by reverse transcription PCR (RT-PCR) and Western blot. The effect of BRD4 silencing plus gemcitabine in TNBC was illustratedin vitro and in vivo.Results:The expression ofBRD4 in TNBC was signiifcantly increased after treatment with gemcitabine.In vitro,BRD4 knockdown signiifcantly lowered the IC50 value. The apoptotic rate of TNBC was signiifcantly increased in theBRD4 silencing plus gemcitabine group compared to the other. The growth rate of tumorin vivo was signiifcantly lowered in the BRD4 silencing plus gemcitabine group.Conclusion:BRD4 may play an important role in the drug resistance to gemcitabine in TNBC.BRD4 silencing plus gemcitabine may be a novel treatment strategy for TNBC.
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Objective To investigate the effect of the dihydroartemisinin (DHA) on the human low-differentiated lung adenocarcinoma cell line A549 and to explore its mechanism. Methods The A549 cells at logarithmic growth phase were divided into control group and DHA group. The cells in the control group were incubated with conventional reagent, and the cells in DHA group were incubated with 500 nmol/L of DHA. After incubation for 72 hours, methyl thiazolyl tetrazolium (MTT) assay was used to examine the proliferation of A549 cells in the two groups. Gene expression of p85, Akt, Bax and Bcl-2 was detected by real-time fluorescence quantitative polymerase chain reaction (PCR) . The protein expression of p85, Akt, p-p85, p-Akt, Bax and Bcl-2 was detected by Western blotting method. The activity of Caspase3 was measured by Caspase3 colorimetric assay kit. Results Compared with the control group, the proliferation rate of A549 cells in DHA group was significantly decreased ( P0.05), but p-p85, p-Akt and Bcl-2 protein expression levels were significantly decreased ( P<0.01) , and Bax protein expression was increased ( P<0.01). Moreover, the activity of Caspase3 was also enhanced ( P<0.001). Conclusion DHA can reduce the proliferation of A549 cells and increase the apoptosis of A549 cells, and its mechanism probably has relationship with the inhibition of PI3K/Akt signaling pathway.
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Objective To invstigate the effect of high dose X-ray irradiation on the expression of multidrug resistance-1 (MDR1), Bcl-2, MMP7 genes. Methods A nasopharyngeal carcinoma cell line,CNE1, were irradiated with a total dose of 50 Gy. The resistance to the cisplatin of CNE1 cells and the irradiated CNE1 (CNE1 R) cells was detected by MTT. mRNAs expression of MDR1 , Bcl-2 and MMP7 was measured by quantitative RT-PCR. Results The expression of MDR1 increased in CNE1 R cells. The semiquantitative A value of MDR1 mRNA was 0.47 ±0.04, and the value of CNE1R cells (1st, 7th, 21st,28th, 35th, 42nd and 49th days after irradiation) were 0.67 ± 0. 06 (t = -5.44, P = 0. 003) ,0.70 ± 0. 01(t=-5.90,P=0. 002),0.73±0. 01(t= -6. 45,P=0. 001) ,0. 67 ± 0. 03 (t= -3.97,P=0.011),0.65 ±0.01(t = -4.43,P=0. 007),0. 62±0. 05(t= -2. 64,P=0.046) and 0.62 ±0.02(t = -3.34,P=0.021), respectively. Bcl-2 mRNA expression were 0.55 ±0.02 and 1.05 ±0.04(t = -9.93,P=0. 000) and MMP7 mRNA expression were 0.51 ±0.01 and 0.82 ±0.02(t = -8.51,P=0.000) in CNE1and CNE1 R cells. Conclusions The MDR1 expression was increased after a total dose of50 Gy irradiation,which may be related to the synchronous change of Bcl-2 and MMP7 genes.