Objective To observe the effect of astaxanthin on radiotherapy sensitivity of lung cancer A549 cells transplanted in nude mice. Methods Twenty BALB/c nude mice were divided into four groups:control group (mice were gavaged with pure water containing with 10% DMSO), astaxanthin group (mice were gavaged with astaxanthin suspension containing with 10%DMSO, astaxanthin was given to mice with the dose of 50 mg/kg on the first day, and every other day in the following days with a total of 7 times), radiotherapy group (mice were gavaged with pure water containing with 10%DMSO, the tumor site was given local radiotherapy with a dose of 5 Gy per time and the total dose was 15 Gy) and combination group (mice were given 50 mg/kg astaxanthin and radiotherapy with 15 Gy total irradiated dose). When the minor axis of the tumor reached 5 mm we began experiment. Tumor growth curve was measured by detecting the line of apsides every other day. Mice were killed on the second day after the last time of astaxanthin administration. Weights of tumor were measured by a balance and then tumor mass was processed into paraffin sections. Expressions of proliferating tumor cell antigen Ki-67, phosphorylated-signal transducers and activators of transcription (p-STAT3), and cell apoptosis (measured by terminal deoxynucleotidyl transferase mediated dUTP nick- end labeling, Tunnel) were detected by immunohistochemistry. Results Compared with control group, the transplanted tumor growth rate slowed down in other three groups (P<0.05), and tumor growth was the most slowly in the combination group. Tumor weight, Ki-67 and p-STAT3 expressions were decreased gradually in turn in control group, astaxanthin group, radiotherapy group and combination group. The anti-tumor rate and percentage of cell apoptosis were increased gradually in turn. There was significant difference between groups by multiple comparison statistics(P<0.05). Conclusion Astaxanthin enhances radiotherapy sensitivity of human lung cancer A549 cells in nude mice by down-regulating the expression of p-STAT3.

AIM:To investigate the impact of excessive endoplasmic reticulum stress on apoptotic cell death in a rat model of chronic cyclosporine A ( CsA ) nephrotoxicity .METHODS: Male Sprague-Dawley rats on a low-salt diet were subcutaneously injected with vehicle (olive oil, 1 mL· kg-1· d-1) or CsA (15 mg/kg) daily for 1 or 4 weeks.Tu-bulointerstitial fibrosis and apoptotic cell death were estimated by trichrome staining and TUNEL staining .In addition , im-munohistochemistry and immunoblotting were used to evaluate the expression of immunoglobulin -binding protein ( BiP) , eu-karyotic initiation factor 2α(eIF2α), growth arrest and DNA damage-inducible protein 153 (GADD153), caspase-12 and caspase-3.RESULTS:The rats treated with CsA for 1 week did not develop tubulointerstitial fibrosis and TUNEL-positive cells, whereas 4-week treatment with CsA induced typical tubulointerstitial fibrosis and increased TUNEL-positive cells. CsA induced a significant increase in BiP and caspase-12 expression peaked at 1 week, and then returned to normal levels at 4 weeks.In contrast, the expression of eIF2α, GADD153 and caspase-3 in CsA-treated rat kidneys were significantly in-creased in a time-dependent manner .CONCLUSION:Excessive endoplasmic reticulum stress causes apoptotic cell death by depleting molecular chaperones and stimulating the proapoptotic pathway in chronic CsA nephrotoxicity .

Objective To investigate the effects of poly adenosine diphosphate ribose polymerase (PARP) inhibitor AG014699 on the proliferation of triple negative breast cancer (TNBC) cell line MDA?MB?231.Methods Cell proliferation and cytotoxicity test kit ( CCK?8) was used to detect the proliferation of MDA?MB?231 cells in different concentrations of AG014699 (0.1,1.0,10.0,20.0 and 40.0 mmol／L), DTX (10－9,10－8,10－7,10－6 and 10－5 mol／L) and CBP (10－6,10－5,10－4 and 10－3 mol／L).Flow cytometry was used to detect cell apoptosis and cell cycle distribution.Results The effects of AG01469 at different concentrations (0.1,1.0,10.0,20.0 and 40.0 μmol／L) on proliferation activity of MDA?MB?231 cells were (94.83 ± 3.93)%, ( 79.42 ± 5.52)%, ( 63.75 ± 4.34)%, ( 38.97 ± 8.42)%, ( 29.70 ± 3.35 )%, with statistically significant differences (F＝75.54,P＜0.01,different concentrations pairwise comparison: all P ＜0.05). The efficacy of AG014699 in combination with DTX at different concentrations (( 69.77 ±17.94)%,(58.34± 2.59)%,( 52.81 ± 2.01)%, ( 41.23 ± 3.38)%, ( 24.82 ± 0.73)%) was compared with that of single DTX (( 81.24 ± 11.91)%, ( 85.74 ± 3.10)%, ( 72.74 ± 4.66)%, ( 55.18 ± 3.19)%, (45.95±3.82)%).The differences were statistically significant (t values were －0.923,－11.748,－6.802,－5.199,－9.410,respectively,with P＞0.05 at 10－9 concentration and P＜0.01 at all other concentrations ). The efficacy of AG014699 combined with CBP ((78.33± 2.89)%,( 60.44± 1.95)%,( 50.55± 3.07)%, (12.07± 1.63)%) and single CBP (( 90.00 ± 6.18)%, ( 87.87 ± 2.30)%,( 76.82 ± 3.37)%,( 40.71 ±1.68)%) was compared,and the cell activity was significantly reduced,indicating statistically significant differences ( t values were －1.935,－15.756,－9.981,－21.192, respectively, and P＞0.05 at 10－6 concentration,P＜0.05 at all the other concentrations ).The q value was＞1.15 when AG014699 was combined with 10－3 mmol／L CBP, which showed synergistic effect.When combined with other effective concentrations of DTX or CBP,the q value was between 0.85 and 1.15,showing additive effect.Conclusion PARP inhibitor AG014699 assisted DTX or CBP can inhibit the proliferation of TNBC cell line MDA?MB?231.By means of simple addition or systematic effect,it can inhibit the triple negative breast cancer.

Carcinoma, Non-Small-Cell Lung ; classification ; therapy ; China ; Humans ; Lung Neoplasms ; classification ; therapy ; Practice Guidelines as Topic ; Receptor Protein-Tyrosine Kinases ; metabolism