Radiosensitivity Of Esophageal Cancer Cells Research Articles

Circ-POSTN promotes the progression and reduces radiosensitivity in esophageal cancer by regulating the miR-876-5p/FYN axis.

Circular RNAs (circRNAs) play critical roles in the tumorigenesis and radiosensitivity of multiple cancers. Nevertheless, the biological functions of circRNA periostin (circ-POSTN) in esophageal cancer (EC) progression and radiosensitivity have not been well elucidated. The expression of circ-POSTN, microRNA-876-5p (miR-876-5p), and proto-oncogene tyrosine-protein kinase (FYN) was analyzed by quantitative reverse transcription PCR (RT-qPCR). Cell proliferation was assessed by MTT, colony formation, and 5-ethynyl-2'-deoxyuridine (EDU) assays. All protein levels were detected by western blot assay. Cell apoptosis and invasion were assessed by flow cytometry analysis and transwell assay, respectively. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the interaction between miR-876-5p and circ-POSTN or FYN. The role of circ-POSTN in vivo was explored by establishing mice xenograft model. Circ-POSTN was overexpressed in EC tissues and cells. Knockdown of circ-POSTN inhibited cell proliferation and invasion and elevated apoptosis and radiosensitivity in EC cells. MiR-876-5p was a direct target of circ-POSTN, and its knockdown reversed the role of sh-circ-POSTN in EC cells. FYN was a direct target of miR-876-5p, and FYN elevation weakened the effects of miR-876-5p overexpression on the progression and radiosensitivity of EC cells. Moreover, circ-POSTN acted as a miR-876-5p sponge to regulate FYN expression. Circ-POSTN interference also suppressed tumor growth and enhanced radiosensitivity in vivo. Circ-POSTN knockdown inhibited proliferation and invasion, but increased apoptosis and enhanced radiosensitivity in EC cells via modulating miR-876-5p/FYN axis, which might be a potential diagnostic and therapeutic target for EC.

Selective nuclear export inhibitor KPT‑330 enhances the radiosensitivity of esophageal carcinoma cells.

Although the concurrent application of definitive chemoradiation has improved the prognosis of patients with esophageal cancer, resistance to therapy poses a major threat to treatment. The present study aimed to investigate whether the use of KPT-330, a selective inhibitor of nuclear export (SINE), enhances the radiosensitivity of esophageal cancer cells. Immunohistochemical staining assays were employed to evaluate the expression and prognostic significance of chromosome maintenance protein-1 (CRM1) in 111 esophageal carcinoma (ESCA) tissues collected from patients with esophageal squamous cell carcinoma. The data showed that the expression of CRM1 in the ESCA tissues was significantly upregulated compared with that in the normal adjacent tissues. Furthermore, patients with higher CRM1 expression had significantly decreased overall survival compared with those with lower CRM1 expression. The effects of KPT-330 and/or radiation on ECA109 human ESCA cells were also evaluated. KPT-330 suppressed the viability of the ECA109 cells. A colony formation assay demonstrated that a combination of KPT-330 and radiation significantly decreased ECA109 cell proliferation. Flow cytometric analysis showed that KPT-330 increased the arrest of the ECA109 cells at the G2/M phase and induced apoptosis. In addition, western blotting revealed that the inhibitory effect of KPT-330 on cell viability was associated with the increased expression of p53 and promotion of the nuclear accumulation of the p53 protein. In conclusion, the present study demonstrated that CRM1 expression is associated with the prognosis of patients with ESCA following radiotherapy. The inhibition of CRM1 expression by the SINE inhibitor KPT-330 increases radiosensitivity and is potentially useful in a combination treatment strategy for esophageal cancers.

Sulconazole Induces PANoptosis by Triggering Oxidative Stress and Inhibiting Glycolysis to Increase Radiosensitivity in Esophageal Cancer

Esophageal cancer is the seventh most common cancer in the world. Although traditional treatment methods such as radiotherapy and chemotherapy have good effects, their side effects and drug resistance remain problematic. The repositioning of drug function provides new ideas for the research and development of anticancer drugs. We previously showed that the Food and Drug Administration-approved drug sulconazole can effectively inhibit the growth of esophageal cancer cells, but its molecular mechanism is not clear. Here, our study demonstrated that sulconazole had a broad spectrum of anticancer effects. It can not only inhibit the proliferation but also inhibit the migration of esophageal cancer cells. Both transcriptomic sequencing and proteomic sequencing showed that sulconazole could promote various types of programmed cell death and inhibit glycolysis and its related pathways. Experimentally, we found that sulconazole induced apoptosis, pyroptosis, necroptosis, and ferroptosis. Mechanistically, sulconazole triggered mitochondrial oxidative stress and inhibited glycolysis. Finally, we showed that low-dose sulconazole can increase radiosensitivity of esophageal cancer cells. Taken together, these new findings provide strong laboratory evidence for the clinical application of sulconazole in esophageal cancer.

HMGB1 induces radioresistance through PI3K/AKT/ATM pathway in esophageal squamous cell carcinoma

BackgroundTo explore the effect of HMGB1 on the radio-sensitivity of esophageal cancer cells through regulating the PI3K/Akt/ATM pathway.Methods and resultsWe observed the expression of HMGB1 and p-ATM in biopsies of esophageal cancer patients with immunohistochemical staining. Western blot and RT-qPCR were applied to detect the protein and RNA related to PI3K/Akt/ATM pathway, respectively. In addition, we inhibited the PI3K/Akt pathway with ly294002 and activated it with IGF1, then we explored the invasion, proliferation ability, and apoptosis of esophageal cancer cells in vitro by transwell, CCK8 assay, and flow cytometry respectively. In vivo, xenograft tumor model was established in nude mice to study the effect of HMGB1 on radioresistance via PI3K/AKT/ATM Signaling Pathway. The survival rate in patients with single positive/double negative expression of HMGB1 and p-ATM was significantly higher than in those with both positive expression of HMGB1 and p-ATM, the depletion of HMGB1 combined with ly294002 significantly inhibited cell proliferation and invasion ability, meanwhile, the addition of IGF1 reversed it. Meanwhile, depletion of HMGB1 and ly294002 promoted apoptosis and arrested the cancer cells in G0/G1 cell cycle with the decreased expression of Cyclin D1 and CDK4 and improved P16. We further validated these results in vivo, the application of HMGB1 silencing promoted apoptosis of xenograft tumors after radiation, especially combined with pathway inhibitor ly294002.ConclusionsEsophageal cancer patients with high expression of HMGB1 and p-ATM have a poor prognosis after chemo-radiotherapy. Down-regulation of HMGB1 may promote the radio-sensitivity of esophageal cancer cells through regulating PI3K/Akt/ATM pathway.

Retraction: Down-regulation of XIAP enhances the radiosensitivity of esophageal cancer cells in vivo and in vitro.

This Retraction follows an Expression of Concern relating to this article previously published by Portland Press.This article is being retracted from Bioscience Reports at the request of the Editor-in-Chief and the Editorial Board following receipt of a notification from a reader, alerting the Editorial Board to the GAPDH Western blots in Figures 1C, 3B and 3E, and the tumor images in Figure 7C which are duplicated in several other publications the same author group, as well as by different authors.The authors have been contacted in regards to the retraction, and have not responded to the Journal's queries and the concerns raised. Given the extent of the issues raised, the Editorial Board stand by the decision to retract the article.

Retraction: Down-regulation of XIAP enhances the radiosensitivity of esophageal cancer cells in vivo and in vitro

Retraction: Down-regulation of XIAP enhances the radiosensitivity of esophageal cancer cells in vivo and in vitro

Effect of Inhibiting DLK1 Expression on Radiosensitivity of Esophageal Cancer Cells

Effect of Inhibiting DLK1 Expression on Radiosensitivity of Esophageal Cancer Cells

Expression of Concern: Down-regulation of XIAP enhances the radiosensitivity of esophageal cancer cells in vivo and in vitro.

Expression of Concern: Down-regulation of XIAP enhances the radiosensitivity of esophageal cancer cells in vivo and in vitro.

Knockdown of FAM83D Enhances Radiosensitivity in Coordination with Irradiation by Inhibiting EMT via the Akt/GSK-3β/Snail Signaling Pathway in Human Esophageal Cancer Cells.

PurposeTo explore the effects of FAM83D on the proliferation, invasion and radiosensitivity of human esophageal cancer cells and to elucidate the mechanism involved in the regulation of the growth and metastasis of esophageal cancer cells.Methods and MaterialsThis study included sixty-nine patients with esophageal cancer. The expression levels of FAM83D in the esophageal cancer tissues and paracarcinoma tissues of the sixty-nine patients were measured. We also examined FAM83D expression in five cell lines. We analyzed the effects of FAM83D on the proliferation, invasion and radiosensitivity of human esophageal cancer cells via MTS, Transwell, and colony formation assays. The effect of FAM83D knockdown on cell apoptosis was assayed by flow cytometry. In addition, we also examined changes in the expression of metastasis-related molecules at the protein and mRNA levels by qRT-PCR and Western blotting after silencing FAM83D expression, and we detected the expression of PI3K/Akt signaling-related proteins by Western blotting.ResultsThe results demonstrated that the expression of FAM83D was obviously higher in esophageal cancer tissues and cell lines than that in human adjacent normal tissues and normal esophageal epithelial cell lines. FAM83D overexpression was positively associated with tumor size, tumor-node-metastasis (TNM) stage, T classification, N classification, distant metastasis and relapse and was negatively associated with patient survival rates. FAM83D shRNA transfection suppressed its expression. Compared to that in the control group, the proliferation of tumor cells in the FAM83D shRNA group was hindered after exposure to radiation in vitro and in vivo; in addition, FAM83D knockdown inhibited cell invasion, induced apoptosis and regulated apoptosis-related protein expression. Moreover, the radiosensitivity of esophageal cancer cells was increased after depletion of FAM83D. In addition, FAM83D silencing was associated with the reversion of EMT, as reflected by an increase in the epithelial marker E-cadherin and a decrease in the mesenchymal markers N-cadherin and vimentin. Further study showed that FAM83D depletion suppressed the signaling pathway involving p-Akt, p-GSK-3β and Snail.ConclusionThe results reveal that FAM83D may be a potential therapeutic target for esophageal squamous cell carcinoma (ESCC) and that lower expression of FAM83D in coordination with irradiation promotes the radiosensitization of ESCC by inducing EMT through the Akt/GSK-3β/Snail signaling pathway.

Silencing of S-phase kinase-associated protein 2 enhances radiosensitivity of esophageal cancer cells through inhibition of PI3K/AKT signaling pathway

We investigated the effect of S-phase kinase-associated protein 2 (SKP2) on radiosensitivity of esophageal cancer (EC) cells. Expression of SKP2, PI3K, AKT, Bcl-2 and Bax were assayed in EC. EC cells were transfected with SKP2-siRNA/IGF-1 to detect expression of SKP2, PI3K, AKT, Bcl-2 and Bax. At last, the radiosensitivity of cells in different doses of X (0, 2, 4, 6, 8 Gy) irradiation and cell apoptosis were also detected. EC cells displayed a higher positive expression rate of SKP2, elevated mRNA and protein expression of SKP2, PI3K, AKT, Bcl-2 and Bax, as well as higher extent of PI3K and AKT phosphorylation. SKP2 silencing downregulated mRNA and protein expression of PI3K, AKT and Bcl-2 but increased p27 protein expression, and inhibited the cell survival rate while promoting cell apoptosis. Taken together, silencing SKP2 can inhibit the PI3K/AKT signaling pathway, thereby increasing the radiosensitivity of EC cells.

Effect of different expression levels of USP28 on apoptosis and related protein expression in esophageal cancer cell ECA109 after irradiation

Objective To observe the effect of different expression levels of USP28 on the radiosensitivity of ECA109 cells by gene transfection method, aiming to provide theoretical basis for comprehensive treatment of esophageal cancer. Methods The expression levels of USP28 and c-Myc in the esophageal epithelial cells Het-1A, ECA109 and ECA109R were quantitatively measured by qRT-PCR. The specific siRNA sequences were designed according to the USP28 and c-Myc genes. The pcDNA-USP28 and pcDNA-c-Myc plasmids were constructed. The esophageal cancer cell ECA109 was transfected with Lipofectamine 2000 to observe the transfection effect and related protein expression. ECA109 and ECA109R cells were exposed to 6 Gy X-ray radiation. The cell apoptosis in each group was detected by flow cytometry. The radiosensitivity was evaluated by clone formation assay. Results The expression levels of USP28 and c-Myc in ECA109 were significantly higher than those in Het-1A (both P<0.05), and the expression levels of USP28 and c-Myc in ECA109R were remarkably higher than those in ECA109(both P<0.05). The pcDNA-USP28 and pcDNA-c-Myc recombinant plasmids were successfully constructed. Compared with the negative control group, the expression of USP28 at the protein and mRNA levels in the si-USP28 group was significantly down-regulated, whereas those in the pcDNA-USP28 group were remarkably up-regulated. Similar results were obtained in terms of c-Myc. Compared with the control group, the expression level of c-Myc protein was significantly up-regulated in the pcDNA-USP28 group, whereas considerably down-regulated in the si-USP28 group. After 6 Gy irradiation, the apoptosis rate and radiosensitivity of ECA109 cells were significantly declined. The apoptosis rate and radiosensitivity of ECA109R cells were increased in the si-USP28 group. Conclusions The expression of USP28 protein is closely correlated with the radiosensitivity of esophageal cancer cells. The underlying mechanism may be related to the regulation of c-Myc expression by USP28. Key words: USP28 gene; c-Myc gene; Esophageal carcinoma cell line; Radiosensitivity

Knockdown of RNF2 enhances the radiosensitivity of squamous cell carcinoma in lung.

A previous study has reported that knockdown of RING finger protein 2 (RNF2) increases the radiosensitivity of esophageal cancer cells both in vitro and in vivo. However, the effect of RNF2 knockdown on radiosensitivity in squamous cell carcinoma (SqCC) remains unknown. For this, NCI-H226 and SK-MES-1 cells were exposed to X-ray irradiation and then RNF2 levels were determined. RNF2 was knocked-down and stable transfectants were selected. Radiosensitivity, cell proliferation, apoptosis, cell cycle, and γ-H2AX foci formation were evaluated. Interaction among ataxia telangiectasia mutated protein (ATM), mediator of DNA damage checkpoint 1 (MDC1), and H2AX were examined. Xenograft models were used to explore the effect of RNF2 knockdown on radiosensitivity in vivo. The results showed that RNF2 expression was significantly increased by X-ray irradiation. RNF2 knockdown combined with X-ray irradiation markedly inhibited cell proliferation, caused cell cycle arrest at the G1 phase, and induced cell apoptosis. In addition, RNF2 knockdown enhanced the radiosensitivity of SqCC cells, inhibited irradiation-induced γ-H2AX foci formation, and impaired the interactions among ATM, MDC1, and H2AX. Furthermore, combination of RNF2 knockdown and X-ray irradiation suppressed tumor growth and promoted tumor cell apoptosis in vivo. RNF2 may be a new therapeutic target to enhance the radiosensitivity of SqCC cells in lung.

Apatinib enhances the radiosensitivity of the esophageal cancer cell line KYSE-150 by inducing apoptosis and cell cycle redistribution.

To determine the radiosensitizing effect of apatinib on esophageal cancer cells, and to preliminarily investigate the underlying mechanism, KYSE-150 cells were treated with apatinib, x-ray or apatinib combined with x-ray, and compared with a blank control. It was observed that apatinib significantly inhibited vascular endothelial growth factor (VEGF) secretion and the proliferation of KYSE-150 cells in a dose-dependent manner. As the concentration of apatinib increased, the radiobiological parameters inactivation dose (D0), quasi domain does (Dq) and survival fraction (SF2) of KYSE-150 cells decreased, while the sensitization enhancement ratio SERD0 increased. The rate of apoptosis in cells treated with apatinib and x-ray was markedly higher compared with those of the blank control, x-ray and apatinib alone groups (P<0.05). The proportion of cells in the G2/M phase was significantly increased in the apatinib, x-ray and combination groups compared with the blank control group (P<0.05). Compared with the control and x-ray groups, combination treatment did not significantly alter the expression level of polyADP-ribose polymerase (PARP), although it significantly increased the expression of cleaved-PARP (P<0.05). Moreover, the expression of cell serine/threonine-protein kinase-2 (CHK2) was downregulated (P<0.05), whilst expression of the phosphorylated form, pCHK2, was significantly increased (P<0.05) in the combination group when compared with the control and x-ray groups. In conclusion, the present study suggested that apatinib increases the radiosensitivity of KYSE-150 esophageal cancer cells by inhibiting VEGF secretion and cell proliferation, and promoting apoptosis and cell cycle redistribution.

Artesunate enhances radiosensitivity of esophageal cancer cells by inhibiting the repair of DNA damage

Radiotherapy plays an important therapeutic role in esophageal cancer (EC). However, acquired radioresistance impairs the efficacy of radiotherapy, often leading to treatment failure. Therefore, it is important to develop novel radiosensitizers to enhance the clinical treatment of EC. The purpose of this study was to investigate the role of artesunate (ART) on radiosensitivity of human EC cell line TE-1. We found that ART inhibited the proliferation of EC cells and enhanced the radiosensitivity of TE-1 cells (SER = 1.24). In vivo tumor growth of xenografts was inhibited markedly by irradiation (IR) combined with ART, with a tumor inhibition rate of 53.76% in IR + ART group vs. 41.13% in IR-alone group. Pretreatment with ART significantly prompted cell apoptosis and reversed the IR-induced G2/M arrest. ART treatment could aggravate DNA damage of EC cells and prolong the formation of γ-H2AX foci induced by IR. ART up-regulated P21 and down-regulated the expression of cyclin D1, RAD51, RAD54, Ku70 and Ku86 protein of irradiated TE-1 cells. These findings support that ART induce radiosensitivity of TE-1 cells in vitro and in vivo, and may prove to be a promising radiosensitizer for EC treatment.

Knockdown of USP28 enhances the radiosensitivity of esophageal cancer cells via the c-Myc/hypoxia-inducible factor-1 alpha pathway.

Acquired radioresistance is a major clinical obstacle in the treatment of esophageal cancer (EC). Ubiquitin-specific protease 28 (USP28) has been implicated in tumor growth in various cancer types. However, the role of USP28 and its underlying mechanisms of radioresistance in EC remain unknown. In the current study, we found that USP28 and c-Myc levels were upregulated in EC tissues and EC cell lines. The mRNA expression levels of USP28 and c-Myc were increased in the radioresistant human EC cell line (ECA109R) compared with those in ECA109 cells. In addition, the expression levels of USP28 and c-Myc were increased with increase in culture time after irradiation. Meanwhile, overexpression of USP28 decreased the radiosensitivity of ECA109 cells. In contrast, USP28 knockdown enhanced the radiosensitivity of ECA109R cells. Moreover, USP28 positively regulated the protein level of c-Myc, and c-Myc negatively regulated the radiosensitivity of ECA109 and ECA109R cells. Furthermore, c-Myc reversed the inhibitory effect of USP28 on the radiosensitivity of EC cells. Additionally, c-Myc enhanced the accumulation of hypoxia-inducible factor-1 alpha (HIF-1α) at the posttranscriptional level, and the reinforcing effect of c-Myc silencing on the radiosensitivity of EC cells could be reversed by HIF-1α overexpression. Besides, knockdown of USP28 blocked the effect of c-Myc on activation of ataxia telangiectasia-mutated/ataxia telangiectasia and Rad3-related DNA damage checkpoint after irradiation. In conclusion, knockdown of USP28 enhanced the radiosensitivity of EC cells by destabilizing c-Myc and enhancing the accumulation of HIF-1α. Therefore, USP28 may serve as a novel therapeutic target to overcome EC radioresistance.

CD59 is a potential biomarker of esophageal squamous cell carcinoma radioresistance by affecting DNA repair

Radiation therapy is an important treatment modality for esophageal cancer. However, acquisition of radioresistance ultimately results in esophageal cancer relapse. CD59, a membrane-bound complement regulatory protein, can transduce signals via a Src kinase in the lipid raft, thus playing a complement-independent role. However, the effect of CD59 on the esophageal cancer response to ionizing radiation remains unclear. In this study, we found that the expression level of CD59 was positively correlated with the radioresistance of esophageal cancer cell lines and clinical specimens. High CD59 expression indicated poor overall survival (OS) and disease-free survival (DFS) in esophageal squamous cell carcinoma (ESCC) patients who received radiotherapy. Genetic alteration of CD59 expression modulated the radiosensitivity of esophageal cancer cells to ionizing radiation. CD59 deficiency exacerbated DNA damage, hindered cell proliferation, and induced G2/M cell cycle arrest and cellular senescence, leading to an impaired DNA damage repair ability. In addition, CD59 deficiency almost completely reduced the phosphorylation of Src at Y416 despite ionizing radiation. A Src inhibitor saracatinib sensitized esophageal cancer cells to irradiation. Therefore, CD59 may be a potential biomarker for predicting the radioresistance of ESCC to radiotherapy.

Inhibition of survivin enhances radiosensitivity of esophageal cancer cells by switching radiation-induced senescence to apoptosis.

PurposeStrategies to increase radiosensitivity are urgently needed. Combining radiosensitizing reagents with radiotherapy could improve the outcome of cancer treatment. Some preclinical studies showed that sepantronium bromide (YM155) could sensitize cancer cells to radiation by inhibiting the survivin protein. In this study, we try to investigate the function of YM155 on radiosensitivity of esophageal squamous cell carcinoma (ESCC) cells.Materials and methodsESCC cell lines were treated with radiation and YM155, and the radiation efficacy was evaluated by cell counting kit-8 assay and clonogenic survival assay. Cell senescence was measured by senescence-associated β-galactosidase staining. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, fluorescein isothiocyanate-labeled Annexin V/propidium iodide assay, and poly ADP-ribose polymerase cleavage were used to detect apoptosis. KYSE150 xenografts model was used to test the efficacy of radiation combined with YM155.ResultsYM155 could inhibit the upregulation of survivin induced by radiation in all ESCC cell lines, but the efficacy of radiosensitization varied in different cell lines. Radiation-induced senescence in KYSE150 and KYSE410 cells, and the combination with YM155 inhibited senescence and promoted apoptosis of ESCC cells, thereby enhancing radiosensitivity. Combination with YM155 and radiation delayed the growth of KYSE150 xenografts in nude mice by switching radiation-induced senescence to apoptosis. When p21 was inhibited in KYSE150 cells, radiation did not induce senescence, and the radiosensitization of YM155 was also attenuated. In KYSE510 and KYSE180 cells, radiation did not induce senescence, and YM155 could not enhance the radiosensitivity.ConclusionOur results suggest a new mechanism that YM155 might sensitize ESCC cells to radiation by switching radiation-induced senescence to apoptosis. The major determinant of radiosensitization by YM155 might be the induction of senescence by radiation.

Knockdown of C1GalT1 inhibits radioresistance of human esophageal cancer cells through modifying β1-integrin glycosylation.

Radiotherapy has played a limited role for the treatment of human esophageal cancer owing to the risk of tumor radioresistance. Core 1 β1, 3-galactosyltransferase (C1GalT1), which catalyzes the formation of core 1 O-glycan structures, is frequently overexpressed during tumorigenesis. However, the exact effects and mechanisms of C1GalT1 in the radioresistance of esophageal cancer remain unclear. In this study, Public databases and our data revealed that C1GalT1 expression was up-regulated in esophageal cancer tissues and was associated with poor survival. Upon irradiation, we found that esophageal cancer cells with high levels of C1GalT1 could tolerate cell death and had increased resistance to radiotherapy. Irradiation also promoted the expression of C1GalT1 and core 1 O-glycan structures. C1GalT1 knockdown increased the radiosensitivity of esophageal cancer cells, and attenuated irradiation-enhanced migration and invasion. Mechanistic investigations showed that C1GalT1 modified O-glycan structures on β1-integrin and regulated its downstream focal adhesion kinase (FAK) signaling. Furthermore, β1-integrin-blocking antibody and FAK inhibitor enhanced radiation-induced apoptosis in esophageal cancer cells. Together, our results indicate that C1GalT1 is a major determinant of radioresistance via modulation of β1-integrin glycosylation. C1GalT1 may be a potent molecular target for enhancing the efficacy of radiotherapy.

Down-regulation of XIAP enhances the radiosensitivity of esophageal cancer cells in vivo and in vitro.

The study investigated the effects of X-chromosome-linked inhibitor of apoptosis (XIAP) gene silencing on the radiosensitivity of esophageal cancer (EC) cells. Western blotting was used to select EC cell lines with XIAP overexpression. Selected EC9706 and KYSE30 cell lines were both divided into four groups: the blank control group, the negative control (NC) group (transfected with pBSHH1), the siRNA-enhanced group (transfected with pBSHH1-XIAP1-siRNA), and the siRNA-decreased group (transfected with pBSHH1-XIAP2-siRNA). Expressions of XIAP were measured by reverse-transcription quantitative PCR (RT-qPCR) and Western blotting, cell survival and viability by MTT assay and colony formation assay, and cell apoptosis by flow cytometry, respectively. Caspase-3 and caspase-9 activity were detected using caspase-3 and caspase-9 activity detection kits. A nude mice model of EC9706 cell line was established to measure tumorigenesis ability. Compared with the NC group, XIAP mRNA and protein expressions were decreased, caspase-3 and caspase-9 activity and apoptosis were up-regulated, and cell survival rate and colony-forming efficiency were lower in the siRNA-enhanced and siRNA-decreased groups in both the cell lines; while the opposite trends were found in the siRNA-decreased group compared with the siRNA-enhanced group. Tumor weight and volume of nude mice were decreased in the siRNA-enhanced and siRNA-decreased groups than those in the NC group, and were elevated in the siRNA-decreased group compared with the siRNA-enhanced group. These results indicate that XIAP gene silencing would strengthen the radiosensitivity of EC9706 cells, which provides a novel target for the treatment of EC.

The medicinal fungus &lt;em&gt;Antrodia cinnamomea&lt;/em&gt; regulates DNA repair and enhances the radiosensitivity of human esophageal cancer cells

This study investigated the adjunctive effects of Antrodia cinnamomea mycelial fermentation broth (AC-MFB), a Taiwanese medicinal fungus, in enhancing the radiosensitivity of esophageal cancer cells. Human CE81T/VGH squamous and BE3 adenocarcinoma esophageal cancer cells were used in this study. A colony formation assay showed that pretreatment with AC-MFB decreased the survival of irradiated esophageal cancer cells, with a maximum sensitizer enhancement ratio of 1.91% and 37% survival. A DNA histogram study showed that AC-MFB pretreatment enhanced cell cycle arrest at the G2/M phase, the most radiosensitive phase. An immunofluorescence assay and a Western blotting assay showed that AC-MFB delayed the abrogation of γ-H2AX, upregulated p21 expression, and attenuated the radiation-induced phosphorylation of ataxia telangiectasia-mutated kinase and checkpoint kinase 2. An in vivo validation study showed that AC-MFB treatment tended to have a synergistic effect with radiation on the tumor growth delay of CE81T/VGH cells in BALB/c mice. These data suggest that this edible fungus product could enhance the effect of radiotherapy against esophageal cancer.