OBJECTIVE: To explore the anti-photoaging properties of salvianolic acid B (Sal B). METHODS: The optimal photoaging model of human immortalized keratinocytes (HaCaT cells) were constructed by expose to ultraviolet B (UVB) radiation. The cells were divided into control, model and different concentrations of Sal B groups. Cell viability was measured via cell counting kit-8. Subsequently, the levels of oxidative stress, including reactive oxygen species (ROS), hydroxyproline (Hyp), catalase (CAT), and glutathione peroxidase (GSH-Px) were detected using the relevant kits. Silent information regulator 1 (SIRT1) protein level was detected using Western blot. The binding pattern of Sal B and SIRT1 was determined via molecular docking. RESULTS: Sal B significantly increased the viability of UVB-irradiated HaCaT cells (P<0.05 or P<0.01). Sal B effectively scavenged the accumulation of ROS induced by UVB (P<0.05 or P<0.01). In addition, Sal B modulated oxidative stress by increasing the intracellular concentrations of Hyp and CAT and the activity of GSH-Px (P<0.05 or P<0.01). The Western blot results revealed a substantial increase in SIRT1 protein levels following Sal B administration (P<0.05). Moreover, Sal B exhibited good binding affinity toward SIRT1, with a docking energy of -7.5 kCal/mol. CONCLUSION Sal B could improve the repair of photodamaged cells by alleviating cellular oxidative stress and regulating the expression of SIRT1 protein.
Humans ; Sirtuin 1/metabolism* ; Ultraviolet Rays ; Oxidative Stress/radiation effects* ; Keratinocytes/metabolism* ; Molecular Docking Simulation ; Benzofurans/pharmacology* ; Skin Aging/radiation effects* ; Reactive Oxygen Species/metabolism* ; Cell Survival/radiation effects* ; HaCaT Cells ; Hydroxyproline/metabolism* ; Glutathione Peroxidase/metabolism* ; Catalase/metabolism* ; Depsides

BACKGROUND: Numerous researches indicated that electromagnetic pulses (EMP) possessed advantages such as strong targeting, minimal side-effects and low treatment cost in tumor therapy, but its optimum parameters for treatment and the relationship between EMP and tumor-derived exosomes remains unclear. This study aims to clarify the effects of EMP with different parameters on the quantity and miRNA (microRNA) of exosomes secreted by human non-small cell lung cancer A549 cells, providing beneficial reference for the clinical application of EMP and related research. METHODS: A549 cells were randomly divided into control group and different EMP radiation groups with respective intensity of 400, 600 and 800 kV/m. EMP was performed with 2000 pulses once, 20 Hz of repetition frequency and 120 ns of pulse width. A549 cells were radiated once per day for continuous 3 days. After radiation, exosomes were collected and identified; cell number was measured by trypan blue staining; the concentration of exosomes was measured by nanoparticle tracking analysis (NTA); the abundance of miRNAs was determined by miRNA sequencing. RESULTS: Compared with control group, the morphology and cell viability of A549 cells in radiation group was not different, but the quantity of exosomes in 400 or 800 kV/m radiation group was significantly decreased (P<0.05), in contrast with obvious increase in 600 kV/m radiation group (P<0.05). The abundance of exosomal miRNAs between control group and each EMP group was obviously different (P<0.05) and target genes of differentially abundant miRNAs enriched in different pathways. CONCLUSIONS Under the experimental condition, the quantity and miRNA abundance of exosomes could be changed by EMP radiation, which could further influence the function of tumor-derived exosomes.
Humans ; Exosomes/genetics* ; A549 Cells ; MicroRNAs/metabolism* ; Lung Neoplasms/pathology* ; Cell Survival/radiation effects* ; Electromagnetic Fields

A contributory role of oxidative stress and protection by antioxidant nutrients have been suspected in cataract formation. Ganoderic acid A (GAA), an effective lanostane triterpene, is widely reported as an antioxidant. The aim of this study is to investigate the potential effects of GAA on cataract formation. After lens epithelial cells (LECs) were exposed to UVB radiation for different periods, cell viability, apoptosis-related protein levels, malondialdehyde (MDA) and superoxide dismutase (SOD) activities were monitored. We found that cell viability, the Bcl-2/Bax ratio and SOD activity were increased, while Cleaved caspase-3 levels and MDA activity were decreased compared with those in UVB-impaired LECs after GAA treated. Furthermore, GAA activated PI3K/AKT in UVB-impaired LECs and effectively delayed the occurrence of lens opacity in vitro. In conclusion, these findings demonstrated that GAA exhibited protective functions in SRA01/04 cells and rat lenses against UVB-evoked impairment through elevating cell viability and antioxidant activity, inhibiting cell apoptosis, activating the PI3K/AKT pathway and delaying lens opacity.
Animals ; Apoptosis ; Cataract/prevention & control* ; Cell Line ; Cell Survival ; Epithelial Cells/radiation effects* ; Heptanoic Acids/pharmacology* ; Humans ; Lanosterol/pharmacology* ; Lens, Crystalline/radiation effects* ; Malondialdehyde/metabolism* ; Rats ; Superoxide Dismutase/metabolism* ; Ultraviolet Rays/adverse effects*

PURPOSE: Hematotoxicity following anti-cancer treatment is known to be related to treatment efficacy in several malignancies. The purpose of this study was to examine the hematologic parameters related to the tumor response and survival in patients treated with curative surgery following preoperative chemoradiotherapy (CRT) for rectal cancer. MATERIALS AND METHODS: Four hundred eighteen patients with rectal cancer who underwent preoperative CRT and curative surgery were analyzed, retrospectively. The main clinical factors and blood cell counts before and after CRT were investigated with respect to their relationships with tumor downstaging and patient survival. RESULTS: The post-CRT leukocyte count was significantly different between the tumor downstaging group and the nondownstaging group (median, 4740/uL vs. 5130/uL; p = 0.013). Multivariate analysis showed that histological grade, circumferential extent, and post-CRT leukocyte count were related to tumor downstaging. In addition, histological grade, post-CRT leukocyte count, and tumor downstaging were related to disease-free survival. The 5-year disease-free survival and overall survival in patients with post-CRT leukocyte count ≤3730/uL, which is the cut-off value derived from the receiver operation characteristic (ROC) curve analysis, were significantly higher than those with higher counts (88.0% vs. 71.6%, p = 0.001; 94.4% vs. 84.1%, p = 0.024). CONCLUSION: Post-CRT leukocyte count of ≤3730/uL could be regarded as a good prognostic factor for tumor response and survival in rectal cancer patients treated with preoperative CRT.
Blood Cell Count ; Chemoradiotherapy* ; Disease-Free Survival ; Humans ; Leukocyte Count ; Leukocytes* ; Leukopenia ; Multivariate Analysis ; Radiation Effects ; Rectal Neoplasms* ; Retrospective Studies ; Treatment Outcome

PURPOSE: Hematotoxicity following anti-cancer treatment is known to be related to treatment efficacy in several malignancies. The purpose of this study was to examine the hematologic parameters related to the tumor response and survival in patients treated with curative surgery following preoperative chemoradiotherapy (CRT) for rectal cancer. MATERIALS AND METHODS: Four hundred eighteen patients with rectal cancer who underwent preoperative CRT and curative surgery were analyzed, retrospectively. The main clinical factors and blood cell counts before and after CRT were investigated with respect to their relationships with tumor downstaging and patient survival. RESULTS: The post-CRT leukocyte count was significantly different between the tumor downstaging group and the nondownstaging group (median, 4740/uL vs. 5130/uL; p = 0.013). Multivariate analysis showed that histological grade, circumferential extent, and post-CRT leukocyte count were related to tumor downstaging. In addition, histological grade, post-CRT leukocyte count, and tumor downstaging were related to disease-free survival. The 5-year disease-free survival and overall survival in patients with post-CRT leukocyte count ≤3730/uL, which is the cut-off value derived from the receiver operation characteristic (ROC) curve analysis, were significantly higher than those with higher counts (88.0% vs. 71.6%, p = 0.001; 94.4% vs. 84.1%, p = 0.024). CONCLUSION: Post-CRT leukocyte count of ≤3730/uL could be regarded as a good prognostic factor for tumor response and survival in rectal cancer patients treated with preoperative CRT.
Blood Cell Count ; Chemoradiotherapy* ; Disease-Free Survival ; Humans ; Leukocyte Count ; Leukocytes* ; Leukopenia ; Multivariate Analysis ; Radiation Effects ; Rectal Neoplasms* ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo assess the effect of Qingfei Quyu Decoction (QQD) in preventing radiation pneumonitis in esophageal carcinoma patients by concurrent using it with chemoradiotherapy.

METHODSA total of 120 patients with mid-late stage esophageal carcinoma were randomly assigned to the treatment group (60 cases) and the control group (60 cases). All patients received concurrent radiochemotherapy. Patients in the treatment group additionally took QQD, one dose per day for 8 successive weeks. The incidence of radiation pneunonitis was compared between the two groups. The improvement rates of short-term benefit rate, Karnofsky performance scale (KPS), and body weight (BW) improvement rate were calculated between the two groups. The 1-and 2-year overall survival rates were compared between the two groups.

RESULTSThe incidence of radiation pneunonitis was 8.93% (15/56) in the treatment group and 18.64% (11/59) in the control group (P < 0.05). The short-term benefit rate was 92.86% (52/56) in the treatment group and 69.49% (41/59) in the control group (P < 0.05). Besides, the KPS and BW improvement rate were higher in the treatment group [89.29% (50/56) and 83.05% (49/59) ] than in the control group [80.36% (45/56) and 66.10% (39/59)] (P < 0.05). The 1-and 2-year overall survival rate were 66.07% and 35.71% in the treatment group, higher than those of the control group (61.02% and 30.51%; P > 0.05).

CONCLUSIONConcurrent using QQD with chemoradiotherapy for treating esophageal carcinoma patients could lower the incidence of radiation pneumonitis, attenuate the degree of radiation induced lung injury, improve clinical benefit rate, and elevate their QOL.

Carcinoma, Squamous Cell ; Chemoradiotherapy ; adverse effects ; Drugs, Chinese Herbal ; therapeutic use ; Esophageal Neoplasms ; drug therapy ; radiotherapy ; Humans ; Radiation Pneumonitis ; prevention & control ; Survival Rate

OBJECTIVETo observe the effect of solar infrared ray (IR) radiation on the expressions of c-Jun and collagens I and III in cultured human skin fibroblasts (HSFs) and explore the molecular mechanism by which IR radiation causes aging of the skin.

METHODSPrimarily cultured HSFs exposed to IR radiation were examined for changes of the cell viability with MTT assay. The mRNA and protein expressions of c-Jun and collagens I and III was detected with real-time quantitative PCR and immunocytochemistry.

RESULTSMTT assay showed that IR irradiation caused inhibition of cell proliferation compared with the control cells. The mRNA and protein expression of collagen I was decreased significantly by IR irradiation with the increase of the irradiation dose (P<0.01). HSFs irradiated by IR for 12 h showed a dose-dependent reduction of the expression of collagen type III mRNA and protein (P<0.05, P<0.01), but the expression increased dose-dependently in response to IR exposure for 24 h (P<0.05 or 0.01). IR irradiation enhanced the mRNA and protein expression of c-Jun in a dose-dependence manner (P<0.05 or 0.01).

CONCLUSIONSIR irradiation can increase the expression of c-Jun, inhibit the expression of collagen I, and cause disturbance in collagen III expression in human skin fibroblasts, which may be one of the mechanism of IR radiation to initiate and promote skin photoaging.

Cell Proliferation ; Cell Survival ; Cells, Cultured ; Collagen Type I ; metabolism ; Collagen Type III ; metabolism ; Fibroblasts ; metabolism ; radiation effects ; Humans ; Infrared Rays ; Proto-Oncogene Proteins c-jun ; metabolism ; RNA, Messenger ; metabolism ; Skin ; cytology ; Skin Aging ; Ultraviolet Rays

OBJECTIVE: To explore the effects of 3-methyladenine (3-MA, an autophagy inhibitor) on sensitivities of nasopharyngeal carcinoma cells to radiotherapy and chemotherapy and the underlying mechanisms.
 METHODS: Cell proliferation was examined by MTT and colony formation assay, while cell apoptosis was evaluated by annexin V/PI double staining and 2-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride (DAPI) staining. Mitochondrial membrane potential was measured by commercial kit (JC-1). The expression of endoplasmic reticulum stress (ERS)-related protein, glucose-regulated protein 78 (GRP78) and autophagy-related protein beclin1, microtubule-associated protein 1 light chain 3 (LC3) were examined by Western blot.
 RESULTS: Cisplatin (DDP), ionizing radiation (IR) or tunicamycin (TM) treatment obviously inhibited the proliferation of HONE-1 cells in a concentration-dependent and time-dependent manner. Compared with control group, pretreatment with 1 mmol/L of 3-MA significantly 
reduced cell viability and enhanced the apoptosis in the DDP (6.00 μmol/L), 4.00 Gy IR or TM (1.00 μmol/L) groups. There was no significant difference in the apoptosis between the DDP (5.8%) and 4Gy IR (6.7%) groups. Compared with the control group, protein levels of GRP78, beclin1 and lipid-conjugated membrane-bound form (LC3-II) were significantly increased after the treatment of DDP, 4.00 Gy IR or TM, which were inhibited by pretreatment of 3-MA.
 CONCLUSION 3-MA can sensitize HONE-1 cells to chemotherapy and radiotherapy, which is related to prevention of endoplasmic reticulum stress-induced autophagy in nasopharyngeal carcinoma cells.
Adenine ; analogs & derivatives ; pharmacology ; Apoptosis ; Apoptosis Regulatory Proteins ; metabolism ; Autophagy ; Beclin-1 ; Carcinoma ; Cell Line, Tumor ; drug effects ; radiation effects ; Cell Proliferation ; Cell Survival ; Cisplatin ; pharmacology ; Endoplasmic Reticulum Stress ; Heat-Shock Proteins ; metabolism ; Humans ; Membrane Potential, Mitochondrial ; Membrane Proteins ; metabolism ; Microtubule-Associated Proteins ; metabolism ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; pathology ; Radiation, Ionizing ; Radiation-Sensitizing Agents ; pharmacology ; Tunicamycin ; pharmacology

OBJECTIVETo study the radiosensitizing effect of resveratrol on hypopharyngeal carcinoma cell line FADU in vitro.

METHODSHypopharyngeal carcinoma cell line FADU was cultured in in vitro DMEM. Its inhibition on cell proliferation was detected using cytotoxicity test (MTT assay). The cell survival curve was drawn using clone formation to obtain sensitive enhancement ratio (SER). Changes of the cell cycle and cell apoptosis were analyzed using flow cytometry (FCM).

RESULTSResults of MTT showed the inhibition of resveratrol on FADU cells increased along with its concentrations (P < 0.05). Results of clone formation indicated the surviving fraction at 2 Gy (SF2) was 0.717 ± 0.062 in the irradiation group, and 0.426 ± 0.035 in the resveratrol plus irradiation group (with SER ranged 1.684 ± 0.178) with statistical difference (P = 0.007). Results of FCM showed that after radiation of 4 Gy radiation, cells at G2/M phase arrest increased, but cells at G1 decreased. After radiation of resveratrol for 24 h, cells at G1 decreased, but cells at G2/M phase and S phase arrest increased. When 4 Gy radiation combined resveratrol was used, cells at G2/M phase arrest significantly increased, but cells at G1 significantly decreased. The apoptosis rate was 1.94% ± 1.65% in the control group, 4.56% ± 0.92% in the irradiation group, 2.03% ± 1.46% in the resveratrol group, and 23.11% ± 7.22% in the resveratrol plus irradiation group. There was statistical difference between the resveratrol plus irradiation group and the rest 3 groups (P < 0.05).

CONCLUSIONResveratrol could enhance the radiosensitivity of hypopharyngeal carcinoma FADU cells in vitro possibly by inducing cell apoptosis and causing changes in the cell cycle distribution.

Apoptosis ; Carcinoma, Squamous Cell ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Head and Neck Neoplasms ; Humans ; Hypopharyngeal Neoplasms ; drug therapy ; Radiation Tolerance ; Radiation-Sensitizing Agents ; therapeutic use ; Stilbenes ; therapeutic use

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and it has a poor prognosis and few therapeutic options. Radiotherapy is one of the most effective forms of cancer treatment, and P53 protein is one of the key molecules determining how a cell responds to radiotherapy. The aim of this study was to determine the therapeutic efficacy of iodine-131 in three human HCC cell lines. METHODS: Western blotting was used to measure P53 expression. The effects of radiotherapy with iodine-131 were assessed by using the clonogenic assay to evaluate cell survival. Flow cytometry was carried out to examine the effects of iodine-131 on cell death, oxidative stress, reduced intracellular glutathione expression, the mitochondrial membrane potential, and the cell cycle. RESULTS: The P53 protein was not expressed in Hep3B2.1-7 cells, was expressed at normal levels in HepG2 cells, and was overexpressed in HuH7 cells. P53 expression in the HuH7 and HepG2 cell lines increased after internal and external irradiation with iodine-131. Irradiation induced a decrease in cell survival and led to a decrease in cell viability in all of the cell lines studied, accompanied by cell death via late apoptosis/necrosis and necrosis. Irradiation with 131-iodine induced mostly cell-cycle arrest in the G0/G1 phase. CONCLUSIONS: These results suggest that P53 plays a key role in the radiotherapy response of HCC.
Apoptosis/*radiation effects ; Blotting, Western ; Carcinoma, Hepatocellular/metabolism/pathology/radiotherapy ; Cell Line, Tumor ; Cell Survival/drug effects ; G1 Phase Cell Cycle Checkpoints/radiation effects ; *Gamma Rays ; Glutathione/metabolism ; Hep G2 Cells ; Humans ; Iodine Radioisotopes/chemistry/pharmacology/therapeutic use ; Liver Neoplasms/metabolism/pathology/radiotherapy ; Phosphorylation ; Reactive Oxygen Species/metabolism ; Tumor Suppressor Protein p53/*metabolism