Cardenolide glycosides sensitize gefitinib-induced apoptosis in non-small cell lung cancer: inhibition of Na+/K+-ATPase serving as a switch-on mechanism.

The treatment of non-small cell lung cancer (NSCLC) is known as a significant level of unmet medical need in spite of the progress in targeted therapy and personalized therapy. Overexpression of the Na+/K+-ATPase contributes to NSCLC progression, suggesting its potentiality in antineoplastic approaches. Epi-reevesioside F, purified from Reevesia formosana, showed potent anti-NSCLC activity through inhibiting the Na+/K+-ATPase, leading to internalization of α1- and α3-subunits in Na+/K+-ATPase and suppression of Akt-independent mTOR-p70S6K-4EBP1 axis. Epi-reevesioside F caused a synergistic amplification of apoptosis induced by gefitinib but not cisplatin, docetaxel, etoposide, paclitaxel, or vinorelbine in both NCI-H460 and A549 cells. The synergism was validated by enhanced activation of the caspase cascade. Bax cleavage, tBid formation, and downregulation of Bcl-xL and Bcl-2 contributed to the synergistic apoptosis induced by the combination treatment of epi-reevesioside F and gefitinib. The increase of membrane DR4 and DR5 levels, intracellular Ca2+ concentrations, and active m-calpain expression were responsible for the caspase-8 activation and Bax cleavage. The increased α-tubulin acetylation and activation of MAPK (i.e., p38 MAPK, Erk, and JNK) depending on cell types contributed to the synergistic mechanism under combination treatment. These signaling pathways that converged on profound c-Myc downregulation led to synergistic apoptosis in NSCLC. In conclusion, the data suggest that epi-reevesioside F inhibits the Na+/K+-ATPase and displays potent anti-NSCLC activity. Epi-reevesioside F sensitizes gefitinib-induced apoptosis through multiple pathways that converge on c-Myc downregulation. The data support the inhibition of Na+/K+-ATPase as a switch-on mechanism to sensitize gefitinib-induced anti-NSCLC activity.

Factors influencing axial elongation in myopic children using overnight orthokeratology.

Several factors influence axial length in children with myopia treated using overnight orthokeratology. To identify these factors, this retrospective study collected axial length and corneal aberration data on 78 eyes before and 1-year after orthokeratology. Patients were divided according to axial elongation (cut-off, 0.25 mm/year). Baseline characteristics included age, sex, spherical equivalent refraction, pupil diameter, axial length, and orthokeratology lens type. Corneal shape effects were compared through tangential difference maps. Group differences in higher-order aberrations of a 4 mm zone were compared at baseline and 1-year following therapy. Binary logistic regression analysis was conducted to identify the variables determined for axial elongation. Significant differences between both groups included the initial age of wearing orthokeratology lenses, type of orthokeratology lens, size of central flattening area, corneal total surface C12 (1-year), corneal total surface C8 (1-year), corneal total surface spherical aberration (SA) (1-year root mean square [RMS] values), change in total corneal surface C12, and change in front and total corneal surface SA (RMS values). The age when wearing an orthokeratology lens was the most important factor influencing axial length in children with orthokeratology-treated myopia, followed by lens type and change in the C12 of the total corneal surface.

Synergistic effects of defocus-incorporated multiple segments and atropine in slowing the progression of myopia.

Myopia is a leading cause of visual impairment in young people worldwide. It sometimes increases the risk of blindness and reduces life quality. Previous reports have revealed the treatment effects of defocus-incorporated multiple segments (DIMS) and topical atropine (ATP) on myopia control. However, no study has evaluated these two interventions together. In this retrospective study, we aimed to determine whether the combination of DIMS lenses and 0.01% ATP can slow the progression of myopia compared with DIMS lenses or single vision (SV) lenses alone. We included 107 children with myopia who were treated with DIMS and 0.01% ATP combination (DIMS + ATP group), DIMS monotherapy (DIMS group), or a control group (SV group). We compared treatment effects among three groups in axial length and myopia progression. After a 1-year follow-up, the DIMS + ATP group showed a smaller change in axial length and myopia progression than the DIMS and SV groups (P < 0.05). Hence, combination treatment with DIMS and 0.01% ATP might be a better choice for children with myopia.

CBCT-based synthetic CT generation using generative adversarial networks with disentangled representation.

BACKGROUND: Cone-beam computed tomography (CBCT) plays a key role in image-guided radiotherapy (IGRT), however its poor image quality limited its clinical application. In this study, we developed a deep-learning based approach to translate CBCT image to synthetic CT (sCT) image that preserves both CT image quality and CBCT anatomical structures. METHODS: A novel synthetic CT generative adversarial network (sCTGAN) was proposed for CBCT-to-CT translation via disentangled representation. The approach of disentangled representation was employed to extract the anatomical information shared by CBCT and CT image domains. Both on-board CBCT and planning CT of 40 patients were used for network learning and those of another 12 patients were used for testing. Accuracy of our network was quantitatively evaluated using a series of statistical metrics, including the peak signal-to-noise ratio (PSNR), mean structural similarity index (SSIM), mean absolute error (MAE), and root-mean-square error (RMSE). Effectiveness of our network was compared against three state-of-the-art CycleGAN-based methods. RESULTS: The PSNR, SSIM, MAE, and RMSE between sCT generated by sCTGAN and deformed planning CT (dpCT) were 34.12 dB, 0.86, 32.70 HU, and 60.53 HU, while the corresponding values between original CBCT and dpCT were 28.67 dB, 0.64, 70.56 HU, and 112.13 HU. The RMSE (60.53±14.38 HU) of sCT generated by sCTGAN was less than that of sCT generated by all the three comparing methods (72.40±16.03 HU by CycleGAN, 71.60±15.09 HU by CycleGAN-Unet512, 64.93±14.33 HU by CycleGAN-AG). CONCLUSIONS: The sCT generated by our sCTGAN network was closer to the ground truth (dpCT), in comparison to all the three comparing CycleGAN-based methods. It provides an effective way to generate high-quality sCT which has a wide application in IGRT and adaptive radiotherapy.

Current Status of Out-of-Hospital Management of Cancer Patients and Awareness of Internet Medical Treatment: A Questionnaire Survey.

Objective: To explore the current situation of the out-of-hospital management of patients with cancer and evaluate the feasibility of Internet medical intervention outside the hospital in China. Methods: The questionnaire was designed based on the investigators' clinical experience, literature data, and the Anderson Symptom Scale, and adopted a cross sectional survey method. Results: Totally 1,171 qualified questionnaires were analyzed. The results showed that 92.7% of patients with cancer experienced varying degrees of out-of-hospital symptoms after treatment, and a third of them needed clinical intervention. Abnormal blood test results outside the hospital were basically consistent with the events that occurred during the hospitalization. One third of patients with cancer could not identify abnormal results. The primary approaches to solve these abnormalities were to seek guidance from the physician in charge or from nearby hospitals, but only 6.75% patients sought help online. More than half of the life or work of patients with cancer are still greatly affected under the current management model. 92% of respondents required medical help outside the hospital, and 65% ones were willing to pay for the out-of-hospital management. Conclusions: Out-of-hospital management model needs to be improved. Most users are willing to accept Internet cancer management with fees. The survey has a positive effect on guiding future Internet cancer management practices in China to a certain extent.

Incidence of chemotherapy-induced nausea and vomiting among cancer patients receiving moderately to highly emetogenic chemotherapy in cancer centers in Sichuan, China.

PURPOSE: Nausea and vomiting are the most painful and feared side effects for patients during chemotherapy. Currently, most studies focus on the occurrence of CINV during the risk phase. We initiated this real-world study to understand the actual occurrence of CINV throughout all phases, to provide a basis to prevent CINV in patients during chemotherapy and improve their quality of life. METHODS: This prospective real-world study was conducted at 17 major cancer centers in Sichuan, China. Cancer patients who were about to receive moderately/highly emetogenic chemotherapy were included in the study. Occurrences of nausea and vomiting were recorded using patient diaries, and physicians are responsible for recording patient clinical data. RESULTS: A total of 1,139 patients were included in this study between August 2018 and April 2019. In this study, the incidence of acute CINV was 55.3%, delayed CINV was 62.3%, and CINV beyond the risk period was 36%. All phases overall, the overall complete control (CC) rate of CINV was 30.1 and 32.1% for highly and moderately emetogenic chemotherapy regimens, respectively. The median CC time for CINV was 7 days, but only 21.5% of these patients used antiemetic regimens according to the NCCN guideline. CONCLUSION: In the real world, the incidence of CINV is high in patients receiving chemotherapy, and nausea and vomiting may occur beyond the risk period; the low level of standardized antiemetic treatment in compliance with the guideline might have been the main reason for unsatisfactory prevention and control of CINV in this study.

Enhanced Photovoltaic Properties of Perovskite Solar Cells by Employing Bathocuproine/Hydrophobic Polymer Films as Hole-Blocking/Electron-Transporting Interfacial Layers.

In this study, we improved the photovoltaic (PV) properties and storage stabilities of inverted perovskite solar cells (PVSCs) based on methylammonium lead iodide (MAPbI3) by employing bathocuproine (BCP)/poly(methyl methacrylate) (PMMA) and BCP/polyvinylpyrrolidone (PVP) as hole-blocking and electron-transporting interfacial layers. The architecture of the PVSCs was indium tin oxide/poly(3,4-ethylenedioxythiophene):polystyrenesulfonate/MAPbI3/[6,6]-phenyl-C61-butyric acid methyl ester/BCP based interfacial layer/Ag. The presence of PMMA and PVP affected the morphological stability of the BCP and MAPbI3 layers. The storage-stability of the BCP/PMMA-based PVSCs was enhanced significantly relative to that of the corresponding unmodified BCP-based PVSC. Moreover, the PV performance of the BCP/PVP-based PVSCs was enhanced when compared with that of the unmodified BCP-based PVSC. Thus, incorporating hydrophobic polymers into BCP-based hole-blocking/electron-transporting interfacial layers can improve the PV performance and storage stability of PVSCs.

Chalcones Display Anti-NLRP3 Inflammasome Activity in Macrophages through Inhibition of Both Priming and Activation Steps-Structure-Activity-Relationship and Mechanism Studies.

Chalcones are responsible for biological activity throughout fruits, vegetables, and medicinal plants in preventing and treating a variety of inflammation-related diseases. However, their structure-activity relationship (SAR) in inhibiting inflammasome activation has not been explored. We synthesized numerous chalcones and determined their SAR on lipopolysaccharide (LPS)-primed ATP-induced NLRP3 inflammasome activation. 11Cha1 displayed good inhibitory activity on release reaction of caspase-1, IL-1ß, and IL-18. It significantly inhibited LPS-induced phosphorylation and proteolytic degradation of IĸB-α and nuclear translocation of NF-ĸB, but had little effect on mitogen-activated protein kinases (MAPKs) activities. Furthermore, 11Cha1 blocked LPS-induced up-regulation of NLRP3, pro-caspase-1, ASC, IL-18, and IL-1ß, indicating the suppression on priming step of inflammasome activation. ASC dimerization and oligomerization are considered to be direct evidence for inflammasome activation. 11Cha1 profoundly inhibited ATP-induced formation of ASC dimers, trimers, and oligomers, and the assembly of ASC, pro-caspase-1, and NLRP3 in inflammasome formation. Decrease of intracellular K+ levels is the common cellular activity elicited by all NLRP3 inflammasome activators. 11Cha1 substantially diminished ATP-mediated K+ efflux, confirming the anti-NLRP3 inflammasome activity of 11Cha1. In summary, the SAR of chalcone derivatives in anti-inflammasome activities was examined. Besides, 11Cha1 inhibited both priming and activation steps of NLRP3 inflammasome activation. It inhibited NF-ĸB activation and subsequently suppressed the up-regulation of NLRP3 inflammasome components including NLRP3, ASC, pro-caspase-1, pro-IL-18, and pro-IL-1ß. Next, 11Cha1 blocked ATP-mediated K+ efflux and suppressed the assembly and activation of NLRP3 inflammasome, leading to the inhibition of caspase-1 activation and proteolytic cleavage, maturation, and secretion of IL-1ß and IL-18.

Discovery of Novel Agents on Spindle Assembly Checkpoint to Sensitize Vinorelbine-Induced Mitotic Cell Death Against Human Non-Small Cell Lung Cancers.

Non-small cell lung cancer (NSCLC) accounts about 80% of all lung cancers. More than two-thirds of NSCLC patients have inoperable, locally advanced or metastatic tumors. Non-toxic agents that synergistically potentiate cancer-killing activities of chemotherapeutic drugs are in high demand. YL-9 was a novel and non-cytotoxic compound with the structure related to sildenafil but showing much less activity against phosphodiesterase type 5 (PDE5). NCI-H460, an NSCLC cell line with low PDE5 expression, was used as the cell model. YL-9 synergistically potentiated vinorelbine-induced anti-proliferative and apoptotic effects in NCI-H460 cells. Vinorelbine induced tubulin acetylation and Bub1-related kinase (BUBR1) phosphorylation, a necessary component in spindle assembly checkpoint. These effects, as well as BUBR1 cleavage, were substantially enhanced in co-treatment with YL-9. Several mitotic arrest signals were enhanced under combinatory treatment of vinorelbine and YL-9, including an increase of mitotic spindle abnormalities, increased cyclin B1 expression, B-cell lymphoma 2 (Bcl-2) phosphorylation and increased phosphoproteins. Moreover, YL-9 also displayed synergistic activity in combining with vinorelbine to induce apoptosis in A549 cells which express PDE5. In conclusion. the data suggest that YL-9 is a novel agent that synergistically amplifies vinorelbine-induced NSCLC apoptosis through activation of spindle assembly checkpoint and increased mitotic arrest of the cell cycle. YL-9 shows the potential for further development in combinatory treatment against NSCLC.

Convolutional neural network-based dosimetry evaluation of esophageal radiation treatment planning.

PURPOSE: A dosimetry evaluation model for treatment planning of esophageal radiation therapy is developed using a deep learning model. The model predicts dose volume histogram (DVH) from distance to target histogram (DTH) based on stacked de-noise auto-encoder (SDAE) and one-dimensional convolutional network (1D-CN). METHOD: First, SDAE is used to extract the features from the curves of DTH and DVH. Then 1D-CN model is employed to learn the relationship between the features of DTH and DVH, and later used to predict the features of DVH from the features of DTH. Finally, the curve of DVH is restored from the features of DVH based on SDAE. Two hundred and seventy treatment plans are used for training 1D-CN and another sixty-three treatment plans are used for evaluating this model. This method is also compared with another two popular prediction methods based on support vector machine (SVM) and U-net. RESULTS: Based on the experimental result, the proposed model achieves the lowest dose endpoint error comparing to the other models. The average prediction error on planned target volume, left lung, right lung, heart, and spinal cord is 2.94% for the proposed model, while the average prediction errors are 6.79% and 3.41% for SVM and U-net, respectively. CONCLUSIONS: A dosimetry evaluation method based on SDAE and 1D-CN is developed in characterizing the correlation relationship between DTH and DVH of treatment plans. The results show that the model could be trained more efficiently in this framework and the DVH could be predicted with higher accuracy comparing to those existing methods. It provides a useful tool in supporting automated treatment planning of esophageal intensity-modulated radiotherapy.

Analysis of amino acids in human tears by hydrophilic interaction liquid chromatography and quadrupole orbitrap mass spectrometry.

Amino acids in human tears play certain physiological roles and their determination is challenging due to complicated chemical properties. This study described a fast and sensitive method for the simultaneous determination of 15 amino acids (AAs) in tears by hydrophilic interaction liquid chromatography and quadrupole orbitrap mass spectrometry (HILIC-Q-Orbitrap-MS). Amino acids in tears were extracted by methanol, and then cleaned up with a solid phase extraction (SPE) cartridge. Chromatographic separation was performed on a 1.7 µm BEH Amide column within 8 min. Tear samples spiked with free AAs were tested in terms of linearity, sensitivity, repeatability, and recovery. Two stable isotope-labeled amino acids were used as internal standards to improve the method performance. Recoveries for all analytes ranged from 89 to 107%. Intra-day and inter-day precision, expressed as relative standard deviations, were all below 10%, and the method detection limits ranged from 0.02 µmol L-1 to 0.11 µmol L-1. The developed method with high throughput and high analyte specificity shows good promise for consistent analysis of free amino acids in tears.

Deep Learning Based Dosimetry Evaluation at Organs-at-Risk in Esophageal Radiation Treatment Planning.

Rapid esophageal radiation treatment planning is often obstructed by manually adjusting optimization parameters. The adjustment process is commonly guided by the dose-volume histogram (DVH), which evaluates dosimetry at planning target volume (PTV) and organs at risk (OARs). DVH is highly correlated with the geometrical relationship between PTV and OARs, which motivates us to explore deep learning techniques to model such correlation and predict DVHs of different OARs. Distance to target histogram (DTH) is chosen to measure the geometrical relationship between PTV and OARs. DTH and DVH features are then undergone dimension reduction by autoencoder. The reduced feature vectors are finally imported into deep belief network to model the correlation between DTH and DVH. This correlation can be used to predict DVH of the corresponding OAR for new patients. Validation results revealed that the relative dose difference of the predicted and clinical DVHs on four different OARs were less than 3%. These promising results suggested that the predicted DVH could provide near-optimal parameters to significantly reduce the planning time.

Favorable progression-free survival in women with two different histopathological subtypes of bilateral breast cancer.

PURPOSE: The aim of this study was to classify bilateral breast cancers (BBCs) into two groups according to histopathological or molecular subtypes of the two breast diseases in each patient and to study their characteristics in relation to survival outcomes. METHODS: Fifty-six BBC patients were enrolled in the study. They were classified according to whether the two breast diseases were of the same or different histopathological subtypes (defined as S-his or D-his groups) and molecular subtypes (defined as S-mole and D-mole groups). Progression-free survival (PFS), overall survival (OS), and important characteristics were then compared between the groups. RESULTS: We observed that the PFS and OS of the S-mole and D-mole groups failed to reach a significant difference. However, D-his BBC patients enjoyed longer PFS than their S-his counterparts, although the OS was similar. To explore the reason for the extended PFS in D-his BBC patients, we first focused on the possible prognostic contribution by various histopathological subtypes in the groups. We compared the proportion of infiltrating ductal carcinoma, infiltrating lobular carcinoma, and other breast cancer subtypes in the D-his and S-his groups, and demonstrated that they were not associated with longer PFS. We then examined age, menopausal status, tumor, node, and metastasis (TNM) stage, expressions of estrogen receptor (ER), progesterone receptor (PR) and Ki67, and metastasis to lymph nodes, viscera, and bone. The results indicated no significant between-group differences in age, TNM stage, ER/PR expression, and metastasis to viscera and bone. However, significantly lower levels of Ki67and decreased lymph node metastasis rate were associated with D-his BBC patients, which might explain the observed longer PFS. CONCLUSIONS: In comparison to S-his, D-his BBC patients had longer PFS, which was associated with lower levels of Ki67 and a decreased lymph node metastasis rate.

CXCR2 is a novel cancer stem-like cell marker for triple-negative breast cancer.

BACKGROUND: Breast cancer is the leading cause of mortality from cancer in women worldwide, and cancer stem-like cell (CSC) is responsible for failure treatment of breast cancer. It plays an important role in resistant disease and metastasis. CD44/CD24 and ALDH are well-accepted protein markers of breast CSC, and it was reported that distinct subtypes of breast CSC were identified by the 2 markers. It is possible that there are various kinds of breast CSC which could be identified by different markers, and CSC markers utilized at present are not enough to fully understand breast CSC. Finding out more novel CSC markers is necessary. CXCR2 is involved in breast cancer metastasis, treatment resistance, and recurrence and has positive cross-talk with known breast CSC protein markers. It can be concluded that CXCR2 is related to breast CSC, and further study is in need. RESULTS: In this study, we assessed expression of CXCR2 with immunohistochemistry in breast cancer tissues from 37 patients and discovered that level of CXCR2 was significantly lower in triple-negative breast cancer (TNBC) compared with non-TNBC. CXCR2 expression decreased in estrogen receptor-negative or HER2-negative breast cancer, but not progesterone receptor-negative counterparts. By immunofluorescence, we observed high coexpression rate of CXCR2 and CSC-related proteins, including NANOG and SOX2. To prove our speculation that CXCR2 was a novel CSC marker for TNBC, we used 4T1 cell, which is a TNBC cell line, to analyze CXCR2-positive subpopulations and observed that CXCR2-positive 4T1 cells showed characteristics of CSC, including resistance to cisplatinum, radiation, and hypoxia, low proportion (around 1%), much more tumor xenografts, tumor spherule formation, and higher levels of CSC-related mRNA compared with CXCR2-negative cells. CONCLUSION: CXCR2 is an acceptable and newly discovered CSC marker for only TNBC.

The use of in-strip digestion for fast proteomic analysis on tear fluid from dry eye patients.

Tear is an accessible fluid for exploring biomarkers of dry eye disease. This study describes a fast proteomic method by LC-Q-orbitrap-MS analysis with in-strip digestion and investigates the tear proteome of dry eye patients. Schirmer's strips were used for collection of tear fluid from patients. These strips were cut into pieces and directly digested with trypsin before mass spectrometry analysis. The data showed that more than 50 proteins were found in tear fluid from dry eye patients. Gene Ontology (GO) annotation showed that most of proteins were transfer/carrier proteins, hydrolyses, enzyme modulators and signaling molecules. Targeted proteomics strategy revealed that 18 proteins were differentially expressed in dry eye patients. Furthermore, it was showed that the common post-translational modification in tear proteins is deamidation of Asn.

Utilization of lung cancer cell lines for the study of lung cancer stem cells.

Lung cancer is one of the most lethal types of cancer, and its poor prognosis is primarily due to drug resistance and cancer recurrence. As it is associated with a low five-year survival rate, lung cancer stem cells (LCSCs) have been the subject of numerous recent studies. For these studies of LCSCs, lung cancer cell lines are more commonly used than lung cancer tissues obtained from patients, as they are easier to acquire. The methods utilized for the identification of LCSCs from lung cancer cell lines include fluorescence activated cell sorting (FACS), magnetic activated cell sorting (MACS), sphere-forming assay and bacterial surface display library screening. As LCSCs have certain proteins expressed on the surface (CD133, CD44 and CD24) or in the cytoplasm (ALDH and ABCG2), which may act as specific markers, the most frequently used technique to identify and obtain LCSCs is FACS. The current lack of recognized biomarkers in LCSCs makes the identification of LCSCs problematic. Furthermore, the various proportions of LCSCs in specific cell lines, as revealed by numerous previous studies, may cause the LCSC model to be questioned with regard to whether the utilization of certain lung cancer cell lines is dependable for LCSC studies. The current review focuses on lung cancer cell lines that are used for the study of LCSCs and the methods available to identify LCSCs with various markers. The present study also aimed to determine the proportion of LCSCs present in specific cell lines reported by various studies, and to discuss the suitability of specific lung cancer cell lines for the study of LCSCs.

TGF-ß1 mediates the effects of aspirin on colonic tumor cell proliferation and apoptosis.

Previous studies have demonstrated that aspirin serves an important role in chemoprevention and the suppression of colorectal cancer (CRC); however, the underlying mechanisms for this inhibition by aspirin remain unclear. Aspirin is capable of promoting apoptosis through prostaglandin-dependent orprostaglandin-independent signaling pathways. In the prostaglandin-dependent pathways, inhibition of cyclooxygenase (COX), particularly COX-2, is the primary mechanism known to be involved in aspirin-induced CRC suppression. Previous studies have implicated prostaglandin-independent signaling pathways and certain associated proteins, including SOX7, in aspirin-induced CRC suppression. In the present study, a newly-characterized association between aspirin, transforming growth factor (TGF)-ß1 and CRC inhibition was identified. Specifically, aspirin triggers CRC cell apoptosis by inducing the secretion of TGF-ß1, and the increased TGF-ß1 then leads to apoptosis and proliferation inhibition in CRC cells.

Aspirin and metformin exhibit antitumor activity in murine breast cancer.

Studies have shown that aspirin and metformin play important roles in chemoprevention and repression of breast cancers, even though the exact mechanism remains unclear. Aspirin is capable of stimulating apoptosis through prostaglandin-dependent or prostaglandin-independent pathways. Metformin inhibits cell growth by enhancing the tumor suppressive function of transforming growth factor (TGF-ß). In the present study, we report a new link between aspirin, metformin, TGF-ß1 and murine breast cancer inhibition. Specifically, we showed that aspirin and metformin enhanced 4T1 cell apoptosis by inducing secretion of TGF-ß1, whereas estradiol weakened the effect.

Zoledronic acid augments the radiosensitivity of cancer cells through perturbing S- and M-phase cyclins and p21CIP1 expression.

Radiotherapy and adjuvant chemotherapy have become the standard treatments for multiple types of cancer. Although cancer cells are usually sensitive to radiotherapy, metastasis and local failure still occur mainly due to developed resistance to radiotherapy. Thus, it is critical to improve therapeutics for cancer treatment. The present study demonstrated that third-generation bisphosphonate zoledronic acid (ZOL), even at a low concentration, augments the radiosensitivity of cancer cells exposed to ionizing radiation (IR) by inducing S-phase arrest and subsequently promoting apoptosis. This function of ZOL was associated with elevated levels of cyclin A and cyclin B in the S and M phases, as well as decreased p21CIP1 expression. In addition, ZOL also inhibited malignant the invasiveness of cancer cells. Notably, these effects could be enhanced concurrently with IR. The present data indicated that combined treatment with ZOL plus IR may be a novel technique to augment the radiosensitivity of cancer cells.