The Expression of BTG2 and Its Regulatory Effect on Radiosensitivity of Lung Adenocarcinoma / 中国生物化学与分子生物学报

Among the types of lung cancer, lung adenocarcinoma accounts for the majority, and its overall survival rate is poor. B-cell translocation gene 2 (BTG2) is a member of the antiproliferative gene family, belonging to the BTG/TOB family. Many studies have shown that BTG2 was abnormally expressed in many types of tumors, but its regulatory role in the radiosensitivity of lung adenocarcinoma remained unclear. In this study, we explored the expression level of BTG2 in patients with lung adenocarcinoma and its correlation with clinical prognosis through online database and tissue samples of lung adenocarcinoma patient. The results indicated that the expression level of BTG2 decreased significantly in lung adenocarcinoma patient with radiation resistance. Bioinformatics analysis confirmed that BTG2 could respond to radiotherapy in lung adenocarcinoma cell lines, and its low expression in lung adenocarcinoma patients was associated with poor prognosis (P < 0.05). The lentivirus overexpressing BTG2 (OE-BTG2) was transfected into human lung adenocarcinoma cell lines to increase the expression level of BTG2 including A549 and H1299. And the effect of BTG2 overexpression on the radiosensitivity of lung adenocarcinoma cell lines was detected by clone formation assay. Clone formation experiment confirmed that overexpression of BTG2 could significantly enhance the radiosensitivity of A549 and H1299 cell lines (P < 0.05). The expression levels of BTG2 and apoptosis related protein-Bax were detected by Western blotting (WB) and immunohistochemistry (IHC). The effect of BTG2 on radiation sensitivity of lung adenocarcinoma was further detected via nude mouse in vivo. WB experiment confirmed that BTG2 upregulation could significantly increase the apoptosis level of A549 and H1299 cells after radiation. Moreover, BTG2 overexpression can markedly enhance the radiosensitivity of lung adenocarcinoma (P < 0.05) and increase the protein level of Bax after radiation in vivo. In conclusion, BTG2 had low expression in lung adenocarcinoma patients and its low expression level was closely related to the poor clinical prognosis. Overexpression of BTG2 can increase the radiosensitivity of lung adenocarcinoma cell lines and promote the process of apoptosis after radiation, indicating a new target for overcoming the radiation resistance of lung adenocarcinoma.

Comparative study on early application of the recipe for activating blood circulation and the recipe for supplementing qi for inhibiting left ventricular remodeling and apoptosis in rats with heart failure / 中国中药杂志

<p><b>OBJECTIVE</b>To compare the characteristics of early application of the recipe for activating blood circulation and the recipe for supplementing qi for inhibiting left ventricular remodeling and apoptosis in rats with heart failure.</p><p><b>METHOD</b>The left coronary artery occlusion was conducted to establish the rat model of heart failure after myocardial infarction. The model rats were randomly divided into 5 groups, including model group, activating blood circulation group (8 g x kg(-1)), supplementing qi group (8 g x kg(-1)), activating blood circulation plus supplementing qi group (16 g x kg(-1)), and captopril group (10.125 g x kg(-1)), and a sham operation group was set up as negative control group. The drugs were administrated on the second day after myocardial infarction with a therapeutic course of 4 weeks or 8 weeks. The heart function was detected by impedance method; Pathological staining and image analysis were used to determine the perimeter and the area of left ventricular cavity, and myocardial nuclei number and collagen content per unit area; Apoptosis percentage of the myocardial cell was detected by TUNEL and the content of Ang II in the cardiac muscle was measured by radioimmunoassay.</p><p><b>RESULT</b>In comparison with the model group, the function of left ventricular contraction function improved, the area of left ventricular cavity diminished, and proliferation of collagen, content of Ang II and apoptosis percentage of the myocardial cell reduced in all of the treatment groups (P < 0.05 or P < 0.01). After treatment of 8 weeks, the activating blood circulation group was similar to the sham operation group in improvement of cardiac index, and decreases of the area of left ventricular cavity and the content of Ang II; Apoptosis percentage of the myocardial cell in the activating blood circulation group was significantly lower than that in the supplementing qi group.</p><p><b>CONCLUSION</b>Both the recipes for activating blood circulation and for supplementing qi can inhibit left ventricular remodeling and myocardial apoptosis, and delay development of heart failure, with the best effect in the activating blood circulation group after treatment of 8 weeks.</p>

Study on cardiac gene expression microarray and recipe for activating blood circulation and supplementing qi on heart of rats with post-infarction heart failure / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of recipe for activating blood circulation and supplementing Qi (RAS) on cardiac functional structure in rats with post-infarction heart failure (PIHF).</p><p><b>METHODS</b>Rat model of PIHF was established by left coronary artery ligation. Left ventricular samples of model rats from infarcted or peri-infarcted area were obtained at PIHF formation stage and stable stage (10 days and 8 weeks respectively after operation), the total RNA extracted and detected using 6 pieces of rat's 40s gene microarray (4096 genes/microarray), the data were analyzed using software as Genespring, Treeview, Clustering and SOM. Besides, RAS was used to treat the model rats beginning from 4 weeks after modeling and lasted for 4 weeks, changes of heart function and cardiac coefficient before and after treatment were observed by impedance method with Captopril as positive control.</p><p><b>RESULTS</b>(1) Genespring analysis showed thousands of genes differential expression (upper or down regulated), including 13 kinds of gene involving energy metabolism, myocardial cytoskeleton, fibrosis, etc. which, in the infarcted area at heart formation stage were 1086 genes and at the stable stage, 724 genes, while in the peri-infarcted area, formation stage 196 genes and stable stage 97 genes. (2) After RAS or Captopril treatment, the heart function improved significantly, with the stroke volume, cardiac output and cardiac index increased significantly (P < 0.01). RAS could also improve the cardiac coefficient of model rats, as compared with that in untreated model, P < 0.01, compared with that in the sham-operated rats, P < 0.05.</p><p><b>CONCLUSION</b>PIHF is a kind of overload heart disease with multiple genes abnormality. RAS could improve the heart function and histologic indexes, so as to treat the heart failure.</p>

Effect of different drug dosage to activate blood circulation and to nourish qi on cardiac function and structure of congestive heart failure rats after acute myocardial infarction / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effect of different drug dosage to activate blood circulation and to nourish Qi on cardiac function and structure of heart failure rats after acute myocardial infarction.</p><p><b>METHOD</b>The congestive heart failure post cardiac infarction rats models subjected to left coronary occlusion were made and given different dosage of drug of Huoxue Yiqi and captopril (positive control) from 4 weeks to 8 weeks after operation. The cardiac function before and after using drugs were observed by impedance methods.</p><p><b>RESULT</b>Treated by different dosage of drug of Huoxue Yiqi and captopil, cardiac function of heart failure rats after acute myocardial infarction improved, SV, CO, CI(P < 0.01); at the same time, prescription of Huoxue Yiqi and Qixue could improve the model rats' heart coefficient, VS SHAM(P > 0.05), but prescription of Yiqi Huoxue and captopril could not improve it.</p><p><b>CONCLUSION</b>Drug to activate blood circulation and to increase qi can treat heart failure rats after acute myocardial infarction, through improving their function and structure. At the same time, more dosage of drug to activate blood circulation and to increase qi(Huoxue/Yiqi drug) may improve the model rats' heart coefficient.</p>