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Autophagy and radioresistance

Gustavo Alencastro Veiga Cruzeiro, Maristella Bergamo Dos Reis, Vanessa Silva Silveira, Régia Caroline Peixoto Lira, Carlos Gilberto Carlotti, Luciano Neder, Ricardo Santos Oliveira, José Andres Yunes, Silvia Regina Brandalise, Simone Aguiar, Agda Karina Eterovic, Luiz Gonzaga Tone, Carlos Alberto Scrideli, Elvis Terci Valera
BACKGROUND: Genetic and epigenetic modifications are closely related to tumor initiation and progression and can provide guidance for understanding tumor functioning, potentially leading to the discovery of new therapies. Studies have associated hypoxia-related genes to tumor progression and chemo/radioresistance in brain tumors. Information on the expression profile of hypoxia-related genes in pediatric medulloblastoma, although scarce, may reveal relevant information that could support treatment decisions...
March 15, 2017: Current Cancer Drug Targets
Yuanyuan Lei, Dan Zhang, Jin Yu, Hui Dong, Jianwei Zhang, Shiming Yang
Cancer stem cells (CSCs), which comprise a small proportion of total cancer cells, have special capacities for self-renewal, differentiation and tumor formation. Currently, CSCs are regarded as the major cause of the failure in anticancer therapy, such as chemoresistance and/or radioresistance, tumor recurrence and metastasis. Autophagy, a process of cellular self-digestion and response to stress, has a role in tumor formation and progression, and it may play a dual role in CSCs-related resistance to anticancer therapy...
February 17, 2017: Cancer Letters
W-X Peng, Y-Y Wan, A-H Gong, L Ge, J Jin, M Xu, C-Y Wu
Although hepatocellular carcinoma (HCC) is usually response to radiation therapy, radioresistance is still the major obstacle that limits the efficacy of radiotherapy for HCC patients. Therefore, further investigation of underlying mechanisms in radioresistant HCC cells is warranted. In this study, we determined the effect of early growth response factor (Egr-1) on irradiation-induced autophagy and radioresistance in HCC cell lines SMMC-7721 and HepG2. We showed that autophagy-related gene 4B (Atg4B) is induced by Egr-1 upon ionizing radiation (IR) in HCC cells...
January 30, 2017: Oncogenesis
Qiong Wang, Zhuya Xiao, Zhenyu Lin, Jie Zhou, Weihong Chen, Wuyun Jie, Xing Cao, Zhongyuan Yin, Jing Cheng
Purpose To investigate the impact of autophagy on the low-dose hyper-radiosensitivity (HRS) of human lung adenocarcinoma cells via MLH1 regulation. Materials and methods Immunofluorescent staining, Western blotting, and electron microscopy were utilized to detect autophagy in A549 and H460 cells. shRNA was used to silence MLH1 expression. The levels of MLH1, mTOR, p-mTOR, BNIP3, and Beclin-1 were measured by real-time polymerase chain reaction (PCR) and Western blotting. Results A549 cells, which have low levels of MLH1 expression, displayed HRS/induced radioresistance (IRR)...
January 24, 2017: International Journal of Radiation Biology
Bing Yao, Bingqian Liu, Lei Shi, Xiang Li, Chuanchuan Ren, Mingbo Cai, Wen Wang, Jianhua Li, Yongde Sun, Yudong Wu, Jianguo Wen
Platelet-activating factor receptor (PAFR) promotes tumorigenesis, angiogenesis and metastasis. Here, we defined the PAFR as a yielding new inhibiting target to selectively enhance the sensitivity of prostate cancer (PCa) cells to radiation. The selective responding to PAFR inhibiter may be caused by the differential expression pattern of PAFR in PCa cells. In this study, we also determined PAFR as a molecular basis by which the radiation induces autophagy suppression independent of activating mTOR pathway...
January 14, 2017: Oncotarget
Francesca Pasi, Lorenzo Fassina, Maria Evelina Mognaschi, Giuseppe Lupo, Franco Corbella, Rosanna Nano, Enrica Capelli
Treatment with pulsed electromagnetic fields (PEMFs) is emerging as an interesting therapeutic option for patients with cancer. The literature has demonstrated that low-frequency/low-energy electromagnetic fields do not cause predictable effects on DNA; however, they can epigenetically act on gene expression. The aim of the present work was to study a possible epigenetic effect of a PEMF, mediated by miRNAs, on a human glioblastoma cell line (T98G). We tested a PEMF (maximum magnetic induction, 2 mT; frequency, 75 Hz) that has been demonstrated to induce autophagy in glioblastoma cells...
2016: Anticancer Research
Jingli Hao, Peter Graham, Lei Chang, Jie Ni, Valerie Wasinger, Julia Beretov, Junli Deng, Wei Duan, Joseph Bucci, David Malouf, David Gillatt, Yong Li
Radioresistance is a major challenge for prostate cancer (CaP) metastasis and recurrence after radiotherapy. This study aimed to identify potential protein markers and signaling pathways associated with radioresistance using a PC-3 radioresistant (RR) subcutaneous xenograft mouse model and verify the radiosensitization effect from a selected potential candidate. PC-3RR and PC-3 xenograft tumors were established and differential protein expression profiles from two groups of xenografts were analyzed using liquid chromatography tandem-mass spectrometry...
September 30, 2016: Oncotarget
Zeng-Fu Shang, Qiang Wei, Lan Yu, Fang Huang, Bei-Bei Xiao, Hongtao Wang, Man Song, Li Wang, Jianguang Zhou, Jian Wang, Shanhu Li
Radiotherapy is promising and effective for treating prostate cancer but the addition of a tumor cell radiosensitizer would improve therapeutic outcomes. PC-1/PrLZ, a TPD52 protein family member is frequently upregulated in advanced prostate cancer cells and may be a biomarker of aggressive prostate cancer. Therefore, we investigated the potential role of PC-1/PrLZ for increasing radioresistance in human prostate cancer cell lines. Growth curves and survival assays after g-ray irradiation confirmed that depletion of endogenous PC-1/PrLZ significantly increased prostate cancer cell radiosensitivity...
September 20, 2016: Oncotarget
Hongxing Ye, Mantao Chen, Fei Cao, Hongguang Huang, Renya Zhan, Xiujue Zheng
BACKGROUND: Glioblastoma is refractory to conventional treatment, which is combined of surgery, chemotherapy and radiotherapy. Recent studies have shown that glioma initiating cells (GICs) contribute to tumorigenesis and radioresistance. Recently, other studies showed that the GICs use the autophagy as the major pathway to survive. Chloroquine, an anti-malarial chemical, is an autophagic inhibitor which blocks autophagosome fusion with lysosome and slows down lysosomal acidification. The aim of this study was to explore the mechanisms of chloroquine on the radiosensitivity of GICs...
September 20, 2016: BMC Neurology
Nancy Berte, Stefanie Lokan, Marcus Eich, Ella Kim, Bernd Kaina
Glioblastoma multiforme (GBM), a malignant brain tumor with a dismal prognosis, shows a high level of chemo- and radioresistance and, therefore, attempts to sensitize glioma cells are highly desired. Here, we addressed the question of whether artesunate (ART), a drug currently used in the treatment of malaria, enhances the killing response of glioblastoma cells to temozolomide (TMZ), which is the first-line therapeutic for GBM. We measured apoptosis, necrosis, autophagy and senescence, and the extent of DNA damage in glioblastoma cells...
October 11, 2016: Oncotarget
Helin Feng, Jin Wang, Wei Chen, Baoen Shan, Yin Guo, Jianfa Xu, Ling Wang, Peng Guo, Yingze Zhang
Osteosarcoma (OS) responds poorly to radiotherapy, but the mechanism is unclear. We found OS tumor tissues expressed high level of protein HIF-1α, a common biological marker indicative of hypoxia. It is known that hypoxic cells are generally radioresistant because of reduced production of irradiation-induced DNA-damaging reactive oxygen species (ROS) in the anaerobic condition. Here we report another mechanism how hypoxia induces radioresistance. In MG-63 human osteosarcoma cells, hypoxic pretreatment increased the cellular survival in irradiation...
June 2016: Journal of Bone Oncology
Wei Wang, Mingbo Liu, Yawei Guan, Qingwu Wu
BACKGROUND MiR-301a and miR-301b are 2 oncomiRs involved in multiple types of cancer. In this study, we explored the expression change of miR-301a and miR-301b in prostate cancer cells in hypoxia and studied their regulation of autophagy and radiosensitivity of prostate cancer cells. MATERIAL AND METHODS QRT-PCR was performed to quantify the expression change of miR-301a and miR-301b in hypoxia. Their effects on autophagy were measured by Western blot analysis, and their effects on radiosensitivity were measured by clonogenic assay and flow cytometry...
June 21, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Lili Song, Shikai Liu, Liang Zhang, Hairong Yao, Fangyuan Gao, Dongkui Xu, Qian Li
MiR-21 is an important microRNA (miRNA) modulating radiosensitivity of cervical cancer cells. However, the underlying mechanism of miR-21 upregulation in radioresistant cervical cancer has not been fully understood. In addition, autophagy may either promote or alleviate radioresistance, depending on the types of cancer and tumor microenvironment. How autophagy affects radiosensitivity in cervical cancer and how miR-21 is involved in this process has not been reported. This study showed that miR-21 upregulation in radioresistant cervical cancer is related to HIF-1α overexpression...
September 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Xi Zhang, Jingfen Ji, Yu Yang, Juan Zhang, Liangfang Shen
Radioresistance has been demonstrated to be involved in the poor prognosis of patients with non-small-cell lung cancer (NSCLC). However, the underlying mechanism remains largely unclear. Investigation on special therapeutic targets associated with radioresistance shows promises for the enhancement of clinical radiotherapy effect toward NSCLC. This study aimed to reveal the role of Stathmin1 (STMN1) in radioresistance in NSCLC as well as the underlying mechanism. Our data showed that the protein levels of STMN1 were significantly upregulated in NSCLC cells subjected to radiation, accompanied with the activation of autophagy...
2016: OncoTargets and Therapy
Feifei Li, Xiaogang Zheng, Yan Liu, Ping Li, Xiongxiong Liu, Fei Ye, Ting Zhao, Qingfeng Wu, Xiaodong Jin, Qiang Li
Unfolded protein response (UPR) is comprised of complex and conserved stress pathways that function as a short-term adaptive mechanism to reduce levels of unfolded or misfolded proteins and maintain homeostasis in the endoplasmic reticulum (ER). UPR can be triggered by prolonged or persistent ER stress under many physiological or pathological conditions, including radiation exposure. Radiation-induced ER stress elicits autophagy and apoptosis in cancer cells, where C/EBP homologous protein (CHOP) and c-Jun NH2-terminal kinase (JNK) may play crucial roles...
May 2016: Radiation Research
Chi Lu, Conghua Xie
Radiotherapy is an important treatment modality for esophageal cancer; however, the clinical efficacy of radiotherapy is limited by tumor radioresistance. In the present study, we explored the hypothesis that radiation induces tumor cell autophagy as a cytoprotective adaptive response, which depends on liver kinase B1 (LKB1) also known as serine/threonine kinase 11 (STK11). Radiation-induced Eca-109 cell autophagy was found to be dependent on signaling through the LKB1 pathway, and autophagy inhibitors that disrupted radiation-induced Eca-109 cell autophagy increased cell cycle arrest and cell death in vitro...
June 2016: Oncology Reports
Otilija Keta, Tanja Bulat, Igor Golić, Sebastien Incerti, Aleksandra Korać, Ivan Petrović, Aleksandra Ristić-Fira
In most patients with lung cancer radiation treatment is used either as single agent or in combination with radiosensitizing drugs. However, the mechanisms underlying combined therapy and its impact on different modes of cell death have not yet been fully elucidated. We aimed to examine effects of single and combined treatments with γ-rays and erlotinib on radioresistant CRL-5876 human lung adenocarcinoma cells with particular emphasis on cell death. CRL-5876 cells were treated with γ-rays and/or erlotinib and changes in cell cycle, DNA repair dynamics, ultrastructure, nuclear morphology and protein expression were monitored at different time points...
2016: Cell Biology and Toxicology
Hao Gu, Mingzhu Liu, Changmao Ding, Xin Wang, Rui Wang, Xinyu Wu, Ruitai Fan
Cancer cells in hypoxia usually make adaptive changes in cellular metabolism, such as altered autophagy. This might be a cause of enhanced radioresistance in some types of cancer. In this study, we investigated hypoxia-responsive miRNAs in two prostate cancer cell lines (DU145 and PC3). This study firstly reported that hypoxia induces further downregulation of miR-124 and miR-144, which might be a result of impaired dicer expression. These two miRNAs can simultaneously target 3'UTR of PIM1. Functional study showed that miR-124 or miR-144 overexpression can inhibit hypoxia-induced autophagy and enhance radiosensitivity at least via downregulating PIM1...
June 2016: Cancer Medicine
Long Wang, Linmei Long, Wenjuan Wang, Zhongqin Liang
Glioblastoma is a malignant human cancer that confers a dismal prognosis. Ionizing radiation (IR) is applied as the standard treatment for malignant gliomas. However, radiotherapy remains merely palliative because of the existence of glioma stem cells (GSCs), which are regarded as highly radioresistant "seed" cells. In this study, the effect and possible mechanisms of radiotherapy in combination with resveratrol (Res) were investigated in a radioresistant GSC line, SU-2. Our results showed that Res inhibited SU-2 proliferation and enhanced radiosensitivity as indicated by clonogenic survival assay...
December 2015: Journal of Pharmacological Sciences
Fei Ye, Ting Zhao, Xiongxiong Liu, Xiaodong Jin, Xinguo Liu, Tieshan Wang, Qiang Li
To explore charged particle radiation-induced long-term hippocampus damage, we investigated the expression of autophagy and antioxidant Nrf2 signaling-related proteins in the mouse hippocampus after carbon ion radiation. Heads of immature female Balb/c mice were irradiated with carbon ions of different LETs at various doses. Behavioral tests were performed on the mice after maturation. Acute and chronic expression of LC3-II, p62/SQSTM1, nuclear Nrf2, activated caspase-3 and the Bax/Bcl-2 ratio were measured in the hippocampi...
December 22, 2015: Scientific Reports
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