Research progress of cell death in radiation protection and radiosensitization / 中国辐射卫生

@#The rapid advances in technology and medicine have greatly facilitated the application of ionizing radiation. Clinically, radiotherapy is one of the major treatments for malignant tumors. However, besides killing tumor cells, ionizing radiation inevitably leads to radiation damage and even death of normal cells. How ionizing radiation causes cell death and the forms of cell death have always been important research topics in this field. Recently, several forms of cell death induced by irradiation have been discovered. Apart from apoptosis, pyroptosis, necroptosis, ferroptosis, autophagic cell death, and methuosis have gradually become research hotspots, and provide new targets for the development of radioprotective drugs and radiosensitizers. In this review, we summarize various forms of ionizing radiation-induced cell death and related molecular mechanisms. We also introduce the latest progress in radiation protection and radiosensitization based on these cell death mechanisms. This review will provide a reference for the research and development of radioprotective drugs and radiosensitizers in the future.

Radiosensitization mechanism of metformin and analysis of clinical application prospect / 中华放射肿瘤学杂志

Metformin is the basic drug for type 2 diabetes mellitus. More and more studies have shown that metformin has anti-tumor effect, and its radiosensitization effect has been gradually found. Metformin can increase the radiosensitivity of tumor cells by improving hypoxia, increasing reactive oxygen species, inhibiting DNA damage repair, inducing cell cycle arrest and regulating immune microenvironment. However, several recently published randomized controlled trials have not confirmed that metformin can increase the efficacy of chemoradiotherapy. In this review, the mechanism and clinical results of metformin radiosensitization were summarized. The dose of metformin will be an important factor for basic and clinical research in the future.

Sulfasalazine increases the radiosensitivity of colorectal cancer cells by promoting ferroptosis / 中华放射肿瘤学杂志

Objective:To investigate the radiosensitization effect of low-dose sulfasalazine (SAS) on colorectal cancer (CRC) cells.Methods:Proliferation inhibition effect of SAS on CRC cells was detected by CCK-8 assay, and the concentration of SAS in vitro assays was based on its IC10 value. CRC cells were treated with SAS alone or combined with inhibitors of apoptosis, autophagy, ferroptosis and necroptosis, then cell viability was detected by CCK-8 assay. Trypan blue staining, clone formation assay and cell growth curves were used to verify the radiosensitization effect of SAS on CRC cells in vitro. CRC cells were treated with SAS and radiotherapy, then the intracellular contents of lipid peroxidation and the protein levels of GPX4, PTGS2, cleaved PARP and active caspase 3 were evaluated, respectively. Subcutaneous xenograft tumor mouse model was established to further verify the radiosensitization effect of SAS in vivo. Results:High dose (lethal dose) of SAS could induce apoptosis and ferroptosis in CRC cells. Low dose (non-lethal dose) of SAS enhanced the radiosensitivity of CRC cells in vitro, and the radiosensitivity effect of SAS could only be abolished by ferroptosis inhibitor (Fer-1). Low dose of SAS combined with radiotherapy significantly down-regulated the expression of GPX4, whereas increased the intracellular lipid peroxidation levels and the expression of PTGS2. SAS also showed significant radiosensitization effect in subcutaneous xenograft tumor model. Conclusion:Our findings suggest that low-dose SAS could increase the radiosensitivity of CRC cells by promoting ferroptosis.

Radiosensitization Effect and Mechanism of Xuefu Zhuyutang on Transplanted Esophageal Carcinoma in Nude Mice / 中国实验方剂学杂志

ObjectiveTo explore the radiosensitization and underlying mechanism of Xuefu Zhuyutang on subcutaneous transplanted esophageal carcinoma. MethodThe subcutaneous xenograft model of human esophageal carcinoma ECA-109 in nude mice was induced and the model mice were divided into a model group， an irradiation group， a Xuefu Zhuyutang group， and a combination group， with six nude mice in each group. After the intervention， the transplanted tumors were removed and weighed， and the tumor inhibition rate of each group was calculated according to the formula. The protein expression of hypoxia-inducible factor-1α （HIF-1α） and vascular endothelial growth factor A （VEGFA） was detected by immunohistochemistry （IHC）. The protein expression of mammalian target of rapamycin （mTOR）， HIF-1α， VEGFA， and vascular endothelial growth factor receptor 2 （VEGFR2） in transplanted tumors was detected by Western blot. The mRNA expression of mTOR， HIF-1α， and VEGFA in transplanted tumors was detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the conditions in the model group， the tumor weight decreased in the irradiation group and the Xuefu Zhuyutang group （P<0.05）， as well as the combination group （P<0.01）. Compared with the irradiation group， the combination group showed decreased tumor weight （P<0.05）， with tumor inhibition rate of 57.37%. Compared with the model group， the irradiation group， the Xuefu Zhuyutang group， and the combination group showed decreased protein expression of VEGFR2， p-mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01） and reduced mRNA expression of mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01）. Compared with the irradiation group， the combination group showed down-regulated protein expression of VEGFR2， p-mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01） and reduced mRNA expression of mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01）. ConclusionXuefu Zhuyutang can inhibit the growth of transplanted esophageal carcinoma ECA-109 in nude mice and shows an obvious radiosensitization effect in combination with radiotherapy. The mechanism may be related to the inhibition of the mTOR/HIF-1α/VEGFA signaling pathway to improve the hypoxic state of tumors.

Research progress on HPV-positive oropharyngeal carcinoma sensitive to radiation therapy / 口腔疾病防治

@#Oropharyngeal carcinoma is a highly heterogeneous disease that is mainly caused by tobacco and alcohol abuse or high-risk human papillomavirus (HPV) infection. HPV-positive oropharyngeal carcinoma and HPV-negative oropharyngeal carcinoma have obvious differences in etiology, epidemiology and prognosis; therefore, different methods should be adopted for treatment. It is known that the TP53 gene is not mutated in HPV-positive oropharyngeal carcinoma, and radiation therapy can activate it and induce cell apoptosis via DNA damage. There are common repair pathways to DNA damage, such as nonhomologous end joining, and this pathway is more sensitive to radiotherapy under the inhibition of HPV oncoprotein. In addition, the further activation of the immune response under the effect of radiation also participates in the elimination of tumors. In this paper, we reviewed the research on the sensitivity of HPV-positive oropharyngeal cancer to radiotherapy to provide a scientific basis for targeted treatment for various pathogenic factors and clinical stages of oropharyngeal cancer in the future.

Preparation and characterization of hollow copper selenide nanomaterials by sacrificial template method / 国际生物医学工程杂志

Objective:To prepare hollow copper selenide nanoparticles (Cu 2- xSe NPs), and investigate their photothermal properties and radiotherapy sensitization performance. Methods:Hollow copper selenide nanoparticles (Cu 2- xSe NPs) were prepared by sacrificial template method with Cu 2O NPs as sacrificial templates and with selenium powder as selenium source. The surface of copper selenide nanoparticles (Cu 2- xSe NPs) was modified with mercapto-ethylene glycol (mPEG-SH) to obtain Cu 2- xSe-PEG NPs. The morphology, particle size and ultraviolet spectrum of the Cu 2- xSe NPs were characterized by transmission electron microscopy, laser particle size analyzer and ultraviolet spectrophotometer. The photothermal properties and radiosensitization performance of the Cu 2- xSe-PEG NPs were investigated by infrared thermal imager and biological X-ray irradiator. Results:The obtained Cu 2- xSe NPs showed a hollow structure and good monodispersity, and the average diameter were (136.9±7.0) nm. The Cu 2- xSe NPs had absorption in the near-infrared region. When the Cu 2- xSe-PEG NPs sample with the mass concentration of 200 μg/ml were irradiated under 808 nm laser at 1.0 W/cm 2 for 10 min, the temperature raised to more than 55 ℃. The level of reactive oxygen species produced by the Cu 2- xSe-PEG NPs under X-ray irradiation was related to the concentration and radiation dose. Conclusions:The proposed preparation method can control the size of synthesized Cu 2- xSe NPs, and the Cu 2- xSe NPs had good photothermal properties and radiosensitization performance. This work will provide a certain theoretical basis for the application of Cu 2- xSe-PEG NPs in tumor thermoradiotherapy.

Research progress of ceria nanoparticles in the field of radiation / 中国辐射卫生

With the rapid development of nuclear technology in the fields of industry and medicine, the possibility of people suffering from radiation damage has also increased. Radiation injury prevention and treatment drugs are the most effective and direct means for the treatment and protection of radiation injury, but the current radiation injury prevention and treatment drugs have limited effects. Due to the unique valence structure of cerium nanomaterials, it has a variety of enzymatic simulation activities and reproducibility. It shows superior oxidation resistance, powerful free radical scavenging function, and can protect cells from radiation damage. It can be used as an ideal it is a radioprotective agent, and is used in a variety of biological fields. A review of relevant literature shows that the antioxidant properties, high SOD mimicking activity, free radical scavenging ability and radiation resistance of ceria nanoparticles are derived from the mutual conversion of Ce3+/Ce4+ and the formation of oxygen vacancies. This article mainly introduces the basis of anti-radiation activity of ceria nanoparticles, radiation protection effects and the research progress of radiotherapy sensitization, and provides theoretical basis and reference for ceria nanoparticles in the field of radiation direction.

Effect of Shengmai Yin on the DNA methylation status of nasopharyngeal carcinoma cell and its radioresistant strains / 药物分析学报

Shengmai Yin (SMY) is a Chinese herbal decoction that effectively alleviates the side effects of radio-therapy in various cancers and helps achieve radiotherapy's clinical efficacy.In this study,we explored the interaction mechanism among SMY,DNA methylation,and nasopharyngeal carcinoma (NPC).We identified differences in DNA methylation levels in NPC CNE-2 cells and its radioresistant cells (CNE-2R)using the methylated DNA immunoprecipitation array and found that CNE-2R cells showed genome-wide changes in methylation status towards a state of hypomethylation.SMY may restore its original DNA methylation status,and thus,enhance radiosensitivity.Furthermore,we confirmed that the dif-ferential gene Tenascin-C (TNC) was overexpressed in CNE-2R cells and that SMY downregulated TNC expression.This downregulation of TNC inhibited NPC cell radiation resistance,migration,and invasion.Furthermore,we found that TNC was hypomethylated in CNE-2R cells and partially restored to a hypermethylated state after SMY intervention.DNA methyltransferases 3a may be the key protein in DNA methylation of TNC.

Ferroptosis, radiotherapy, and combination therapeutic strategies

Ferroptosis, an iron-dependent form of regulated cell death driven by peroxidative damages of polyunsaturated-fatty-acid-containing phospholipids in cellular membranes, has recently been revealed to play an important role in radiotherapy-induced cell death and tumor suppression, and to mediate the synergy between radiotherapy and immunotherapy. In this review, we summarize known as well as putative mechanisms underlying the crosstalk between radiotherapy and ferroptosis, discuss the interactions between ferroptosis and other forms of regulated cell death induced by radiotherapy, and explore combination therapeutic strategies targeting ferroptosis in radiotherapy and immunotherapy. This review will provide important frameworks for future investigations of ferroptosis in cancer therapy.

Low-glucose combined with palmitic acid enhances the radiosensitivity of colorectal cancer through inducing reactive oxygen species generation and DNA damage / 中华放射肿瘤学杂志

Objective:To investigate the mechanism underlying the inhibiting effect of low-glucose combined with palmitic acid on human colon cancer cells and its influence on the radiosensitivity.Methods:Under the treatment of low-glucose, palmitic acid and low-glucose combined with palmitic acid, the treatment condition that significantly inhibited the proliferation of SW480 was screened by CCK-8 assay. The reactive oxygen species (ROS) level, mitochondrial membrane potential and apoptosis rate were detected by flow cytometry. The changes in the radiosensitivity were detected by immunofluorescence-based γ-H 2AX quantification and colony formation assay. The protein expression level was detected by Western blot. Results:Compared with the control group, the condition of low-glucose combined with 120μmol/L palmitic acid significantly inhibited the proliferation of SW480 cells ( P<0.01). The expression levels of CPT1a, PFKFB3 and PKM were significantly up-regulated, the expression levels of NDUFV1, NDUFV2 and NDUFS1 were remarkably down-regulated, the ROS level was significantly increased and the ATP level was considerably reduced in the cells under metabolic stress (all P<0.01). After irradiation, the number of γ-H 2AX foci was significantly increased ( P<0.05), and the D 0 value was significantly reduced ( P<0.01), the ROS level was considerably increased ( P<0.001), the apoptosis rate was significantly increased ( P<0.001) and the expression level of γ-H 2AX protein was remarkably up-regulated ( P<0.01) in the low-glucose combined with 120μmol/L palmitic acid group. Pretreatment with NAC could reverse the changes of ROS, apoptosis and γ-H 2AX protein expression. Conclusions:The combination of low-glucose and palmitic acid can induce metabolic stress in SW480 cells, inhibit tumor proliferation and increase the radiosensitization when combined with radiotherapy by inducing the generation of ROS and DNA damage.

Screening of differentially expressed miRNAs in A549 cells induced by 17-AAG-M and its effect on radio-sensitivity / 中华放射肿瘤学杂志

Objective:To screen 17-AAG-M-induced differentially expressed miRNAs in human non-small cell lung cancer (NSCLC) A549 cells under X-ray and evaluate its effect on radio-sensitivity.Methods:A549 cells were treated with 17-AAG-M and 4 Gy. Total RNA was extracted for microarray screening. The expression of the miRNAs of interest in the tumor was observed by public database. The target miRNAs were analyzed by using GO and KEGG pathways, and verified by qPCR. The effect of target miRNAs on the survival rate and proliferation of A549 cells under X-ray was evaluated by MTT and clone formation assays. The radio-sensitivity of the target miRNAs was analyzed by the single-hit multi-target model formula.Results:20 differentially expressed miRNAs were screened. The down-regulated hsa-miR-30a-3p showed a close correlation with lung cancer in the database. It was involved with 50 biological processes including cell proliferation and affected the MAPK signaling pathway, cancer-related pathways and cell cycle, etc. Compared with the 17-AAG-M group, the relative expression level of hsa-miR-30a-3p under the action of 17-AAG-M and X-ray was down-regulated from 2.42 to 0.16. hsa-miR-30a-3p inhibited the survival rate of A549 cells (survival rate: 78.52%) and further decreased to 69.00% under X-ray. Up-regulation of hsa-miR-30a-3p expression inhibited the proliferation of tumor cells and increased the radio-sensitivity of A549 cells. The radio-sensitization ratio was 1.18. The above performance became more obvious under the action of 17-AAG-M.Conclusions:In A549 cells, hsa-miR-30a-3p is differentially expressed under the action of 17-AAG-M and X-ray. Moreover, up-regulation of the expression level of hsa-miR-30a-3p in A549 cells can reduce the viability and proliferation of tumor cells, and increase the radio-sensitivity of tumor cells. The inhibition effect of X-ray combined with 17-AAG-M upon tumors can be strengthened.

Research progress in the molecular mechanisms of histone deacetylase inhibitors for radiosensitization / 中华放射医学与防护杂志

Radiotherapy is one of the most commonly used and effective method to treat malignant tumors in clinical practice. However, there are still some limitations including high radiotherapy doses, harmful side effects on normal tissues, and radiation resistance of tumor cells. Therefore, seeking safe and effective radiotherapy sensitizers to improve radiation sensitivity of tumor cells has been focused for a long time. Histone deacetylase inhibitors (HDACIs), as a kind of epigenetic modifiers, can regulate the sensitivity of tumor cells to ionizing radiation and ultraviolet radiation in addition to the inherent anticancer characteristics. This article reviewed the molecular mechanisms of HDACIs in enhancing radiation sensitivity and by selectively killing tumor cells.

Radiosensitization effect of Ta 4C 3-PVP nanosheets on xenograft tumor in mice bearing 4T1 murine triple-negative breast cancer / 中华放射医学与防护杂志

Objective:To investigate the radiosensitizing effect of Ta 4C 3-PVP nanosheets on the tumor of 4T1 murine triple-negative breast cancer cells planted in mice. Methods:4T1 tumor-bearing mice model was established by subcutaneous injection of 4T1 cells into the right flank of the female BALB/c mice. The mice were divided into four groups uniformly according to their tumor size: blank control group, Ta 4C 3-PVP group, ionizing radiation (IR) group and Ta 4C 3-PVP plus IR group. A single dose of 8 Gy X-ray local irradiation was given to xenograft tumor at 24 h after tail intravenous injection of Ta 4C 3-PVP (20 mg/kg). The xenograft tumor volume and weight, the pathological changes of tumor tissue, the expression of tumor proliferative marker Ki-67 protein, and the formation of γ-H2AX foci [a DNA double-strand breaks (DSBs) molecular marker] were detected. Tumor growth curve was established, and enhancement factor (EF) and tumor inhibition rate were calculated. Results:Compared with the blank control group, tumor growth was significantly inhibited ( t=5.41, 9.59, P < 0.05) and tumor weight was markedly decreased ( t=2.67, 4.40, P < 0.05) in both IR group and Ta 4C 3-PVP plus IR group at day 16 after IR. The EF in Ta 4C 3-PVP plus IR group was 1.57, and tumor inhibition rate in Ta 4C 3-PVP plus IR group were about 64%, which was much higher than that of IR group alone(42%). Immunohistochemistry and immunofluorescence histochemistry assays showed that the expression of Ki-67 protein was obviously decreased and the amount of γ-H2AX foci was significantly increased in both IR group and Ta 4C 3-PVP plus IR group in comparison with the blank control group ( t=5.73, 8.02, 2.97, 9.86, P < 0.05). Moreover, the inhibition of Ki-67 protein expression and the increase of γ-H2AX foci were much higher in Ta 4C 3-PVP plus IR group than that in IR group ( t=4.75, 4.42, P < 0.05). Conclusions:Ta 4C 3-PVP nanosheets could enhance radiosensitivity of xenograft tumor in 4T1 tumor-bearing mice through increasing the IR-induced DNA DSBs.

Effect of Astragalus Polysaccharide on Radiosensitivity and Epithelial-mesenchymal Transition of Human Nasopharyngeal Carcinoma CNE-1 Cells / 中国实验方剂学杂志

Objective:Astragalus polysaccharide (APS) was used in combination with ionizing radiation (IR) to investigate the mechanism of APS on the radiosensitivity of human nasopharyngeal narcinoma CNE-1 cells and the epithelial-mesenchymal transition (EMT). Method:Cell counting kit-8 (CCK-8) was used to detect the cytotoxicity of different concentrations of APS (0，6.25，12.5，25，50，100，200 g·L-1) on CNE-1 cells. Colony formation assay was used to calculate the survival fraction (survival fraction, SF) of CNE-1 cells treated with 12.5 g·L-1 APS combined with different radiation doses (0，2，4，6 Gy). The linear quadratic equation mathematical model (LQ) was used to draw the radiosensitivity curve according to SF value. Cell scratch and transwell chamber test were used to detect the migration and invasion ability of cells in each group. The apoptosis of cells in each group was detected by flow cytometry, Western blot was used to detect the expressions of EMT markers, apoptosis markers and protein kinase B/extracellular regulated protein kinases (Akt/ERK) pathway proteins in each group. Result:The results of colony formation assay and radiosensitivity curve showed that the combination of non-toxic dose of 12.5 g·L-1 APS and radiation dose of 4 Gy could significantly increase the radiosensitivity of CNE-1 cells. Compared with blank group and IR group, APS combined with IR could significantly inhibit the migration and invasion of CNE-1 cells (P<0.05), and increase the rate of apoptosis (P<0.05). In addition, compared with the blank group and the IR group, APS combined with IR could significantly down-regulate the expressions of N-cadherin, p-Akt and p-ERK, and significantly up-regulate the expressions of E-cadherin, Bax and Caspase-3 (P<0.05). Conclusion:APS combined with IR can inhibit the migration and invasion of CNE-1 cells, and increase the apoptosis induced by radiotherapy, which may be related to the inhibition of EMT and Akt/ERK pathway.

Radiosensitization and micro CT imaging of multifunctional gold nanoparticles in lung adenocarcinoma A549 cell: an in vivo animal study / 中华放射肿瘤学杂志

Objective To evaluate the radiosensitization effect and micro CT imaging of multifunctional gold nanoparticles in lung adenocarcinoma A549 tumor-bearing mouse models.Methods The tumor-bearing mice were injected with gold nanoparticles and irradiated with different energy levels of 160 kV and 6 MV X-ray.The tumor volume changes were measured.Intra-tumoral injection of gold nanoparticles was administered and micro CT scan was performed at different time points to observe the imaging and retention time of gold nanoparticles in the tumor tissues.Results The tumor volume did not significantly differ between the control and gold nanoparticles groups (P=0.941).The tumor volume in the 6 MV X-ray combined with gold nanoparticles group was slightly reduced compared with that in the 6 MV X-ray group with no statistical significance (P=0.730).The tumor volume in the 160 kV X-ray combined with gold nanoparticles group was significantly smaller than that in the 160 kV X-ray group (P=0.026).Micro CT scan demonstrated that gold nanoparticles could be deposited in the tumors for 30 d and yielded excellent imaging effect.No gold nanoparticles-induced toxicity was observed.Conclusions Multifunctional gold nanoparticles exert significant radiosensitization effect in the lung adenocarcinoma A549 transplanted tumors irradiated with 160 kV X-ray.Stable CT imaging of the gold nanoparticles-injected tumors can be used as a potential method for mapping and delineating the target area in tumor-guided radiotherapy.

Research progress on radioresistance and sensitization of tumor cells in three-dimensional culture system / 中华放射肿瘤学杂志

Three-dimensional cell culture is a novel type of in vitro culture method.This system can mimic the microenvironment of cell growth in vivo,where cells exhibit similar state and function to that in the in vivo environment.Currently,three-dimensional culture system has been widely applied in tissue engineering and tumor cell biology fields,etc.Radiotherapy is an important treatment of cancer.Radioresistance of tumor cells is the main cause of treatment failure,tumor recurrence and metastasis.Tumor cells can exhibit the resistant characteristics in the three-dimensional culture system,similar to those of tumor cells in vivo.Therefore,three-dimensional culture system can be adopted to investigate the radioresistance and underlying mechanism of tumor cells and identify the key factors regulating the radioresistance of tumor cells,which plays a pivotal role in enhancing the radioresistance and improving the effect of radiotherapy.This article will review recent research progress in the radioresistance and sensitization of tumor cells under three-dimensional culture system,aiming to provide reference for relevant investigations.

Effect and mechanisms of curcumin on the radiosensitivity of human ACHN renal cell carcinoma xenografts / 西安交通大学学报(医学版)

Objective: To investigate the effect and mechanisms of curcumin on the radiosensitivity of human ACHN renal cell carcinoma xenografts. Methods: ACHN cells were xenografted into nude mice subcutaneously. Preliminary experiments were conducted to observe the tolerance of curcumin and radiation, and the appropriate dose of curcumin for subsequent experiments was selected. The nude mice were divided into different groups randomly. Tumor growth was monitored following intervention. The radiosensitization ratio (E/O) of curcumin and tumor inhibition rate were calculated. Flow cytometry was employed to detect apoptosis of xenografts cells in different groups. The expression of NF-κB signaling related proteins in ACHN cells and xenografts was detected by Western blot. Results: The method of tumor cell suspensions inoculation manifested a good tumor-take rate of 85.7%. Curcumin (25 mg/kg) could enhance the radiosensitivity of ACHN transplanted human renal carcinoma in nude mice. The E/O ratio was 1.64 (>1.4). Compared with that in the radiation group, the apoptosis rate in curcumin + radiation group was markedly increased (P<0.05). The expression levels of NF-κB, DNA-PKcs and downstream regulatory proteins, including VEGF, COX2 and Bcl-2, were obviously suppressed by curcumin in combination with IR treatment (all P<0.05 vs. IR group). Conclusion: Curcumin enhanced radiosensitivity of ACHN RCC xenografts by inhibiting DNA damage repair, inducing apoptosis and suppressing IR-induced NF-κB signaling.

Radiosensitizion effect of stattic on the xenograft of ECA109 esophageal cancer cells in nude mice / 中华放射医学与防护杂志

Objective To investigate the radiosensitization effect of stattic on the xenograft of esophageal squamous cell carcinoma ( ESCC ) ECA109 cells in nude mouse and explore the underlying mechanisms. Methods Male nude mice inoculated subcutaneously with ECA109 cells were used to examine the radiosensitization effect of stattic in vivo. When average volume of tumors was about 150 mm3 , mice were randomly divided into 4 groups:control group, 25 mg/kg stattic alone group, ionizing radiation (IR) (6 Gy) alone group, and 25 mg/kg stattic plus IR group. During the term of treatment, the volume of tumors was measured every 2 days. On 25 days after treatment, the mice were killed and the expressions of pSTAT3, STAT3, HIF-1α and VEGF in ECA109 xenografts were assessed by Western blot and immunohistochemistry analysis. Results The volume of tumor in nude mice was (705. 1 ± 75. 5) mm3 in stattic plus IR group, which was significantly smaller than that in IR group (113. 5 ± 101. 4) mm3 and stattic alone group(1696.5 ±100.6)mm3(t=4.35, 14.14,P<0.0). The inhibition rate was (66.1 ± 3. 2)％ in stattic plus IR group. The expression levels of pSTAT3, HIF-1α and VEGF were obviously decreased in the stattic plus IR group compared with other groups (t=17. 07, 5. 05, 3. 54, P<0. 05). Conclusions Stattic play a radiosensitization role in the xenograft of esophageal carcinoma in nude mice probably by inhibiting the signaling pathways of pSTAT3, HIF-1α and VEGF.

Radiosensitive effect of gold nanoparticles on lung cancer A549 cells / 中华放射医学与防护杂志

Objective To study the radiosensitization effect of thio-glucose capped gold nanoparticles (Glu-GNPs) on human lung adenocarcinoma A549 cells in vitro.Methods Human lung adenocarcinoma cell line A549 in logarithmic phase was divided into four groups:control group,drug group (Glu-GNPs),irradiation group (irradiation of 6 MV group and irradiation of 160 kV group),Glu-GNPs combined irradiation group (6 MV + Glu-GNPs group,160 kV + Glu-GNPs group).Transmission electron microscopy (TEM) was used to observe the distribution of Glu-GNPs in cells.Toxicity of Glu-GNPs on A549 cells and the inhibitory effect of Glu-GNPs combined with irradiation on cell proliferation were determined using crystal violet assay.Clonogenic assay were performed to evaluate radiosensitization of Glu-GNPs on A549 cells.Immunofluorescence assay of γ-H2AX,a biomarker of DNA damage that underlies cellular response to irradiation was used to evaluate radiation-induced DNA double-strand break (DSB).Results TEM images showed that Glu-GNPs were mainly distributed in the cytoplasm of A549 cells,including endosomes and mitochondria.Glu-GNPs had little cytotoxicity toward A549 cells with a concentration lower than 100 nmol/L.Different concentrations (0-100 nmol/L)of Glu-GNPs combined with different energy of X-rays had significant inhibitory effects on A549 cells.Under 160 kV and 6 MV X-ray conditions,the Glu-GNPs treatment further decreased the survival fraction of irradiation group (P ＜ 0.05),and the sensitizing enhancement ratio (SER) was 1.41 and 1.15,respectively.Moreover,Glu-GNPs significantly increased radiation-induced γ-H2AX foci in A549 cells,and the number of γ-H2AX foci with 160 kV X-ray radiation was higher than that with 6 MV X-ray radiation (t =12.392,14.893,18.947,P ＜ 0.05).Conclusions Uptake of Glu-GNPs by A549 cells could enhance radiation effects,especially for kilovolt X-ray radiation.

Research advances in tumor radiosensitization mediated by topoisomerase inhibitors / 中华放射医学与防护杂志

As anticancer drugs,topoisomerase inhibitors have been widely used in clinical practice,and their radiosensitivity has been gradually recognized.Many topoisomerase inhibitors are currently in pre-clinical and clinical studies.Several studies have shown that some topoisomerase inhibitors may be potential ideal radiosensitizers.However,the physico-chemical properties,toxicity and sensitization effects should be further investigated.