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Autophagy and chemoresistance

Jin-Cheng Huang, Zhi-Fei Cui, Shui-Mu Chen, Lian-Jun Yang, Hong-Kai Lian, Bin Liu, Zhi-Hai Su, Jin-Shi Liu, Min Wang, Zheng-Bo Hu, Jia-Yao Ouyang, Qing-Chu Li, Hai Lu
Osteosarcoma(OS) remains a major health concern in childhood and adolescence, although cisplatin is one of the gold standard chemotherapeutic drugs in the treatment of OS, chemoresistant to cisplatin is common. Phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin inhibitor (mTOR) pathway and autophagy regulates chemosensitivity incancer cells. In this study, we hypothesized that NVP-BEZ235, a dual inhibitor of PI3K/mTOR, could synergize cisplatin sensitivity in OS. In vitro , NVP-BEZ235 plus cisplatinexerted a synergistic effect on cell proliferation inhibition and apoptosis induction...
February 13, 2018: Oncotarget
Dongfang Tang, Ruyong Yao, Dandan Zhao, Lin Zhou, Yun Wu, Yang Yang, Yifeng Sun, Liming Lu, Wen Gao
Insulin-like growth factor (IGF) signaling plays an important role in tumorigenesis and metastasis. Here, we analyzed insulin-like growth factor (IGF) binding protein-2 (IGFBP2) expression in 81 lung cancer patients and 36 controls consisting of healthy and benign pulmonary lesion participants for comparison, then validated the IGFBP2 expression in additional 84 lung cancer patients, and evaluated the prognostic and chemoresistant significance of IGFBP2 in two cohorts respectively. Next we detected the reversal effect of trichostatin A (TSA) on chemoresistance in cell lines with high IGFBP2 expression...
March 2, 2018: Scientific Reports
Kai Zhang, Jing Chen, Hao Zhou, Ying Chen, Yingru Zhi, Bei Zhang, Longbang Chen, Xiaoyuan Chu, Rui Wang, Chunni Zhang
Sorafenib is currently the only systemic agent approved for treatment of advanced hepatocellular carcinoma (HCC). However, intrinsic and acquired resistance to sorafenib remains a great challenge with respect to improving the prognoses of patients with HCC. The cyto-protective functions of autophagy have been suggested as a potential mechanism by which chemoresistance or targeted drug resistance occurs in tumour cells. In the present study, miR-142-3p was identified as a novel autophagy-regulating microRNA (miRNA) that plays a vital role in sorafenib resistance in HCC cells...
February 22, 2018: Cell Death & Disease
Chandan Kanta Das, Benedikt Linder, Florian Bonn, Florian Rothweiler, Ivan Dikic, Martin Michaelis, Jindrich Cinatl, Mahitosh Mandal, Donat Kögel
Target-specific treatment modalities are currently not available for triple-negative breast cancer (TNBC), and acquired chemotherapy resistance is a primary obstacle for the treatment of these tumors. Here we employed derivatives of BT-549 and MDA-MB-468 TNBC cell lines that were adapted to grow in the presence of either 5-Fluorouracil, Doxorubicin or Docetaxel in an aim to identify molecular pathways involved in the adaptation to drug-induced cell killing. All six drug-adapted BT-549 and MDA-MB-468 cell lines displayed cross resistance to chemotherapy and decreased apoptosis sensitivity...
February 17, 2018: Neoplasia: An International Journal for Oncology Research
Lei Tian, Zhifeng Zhao, Ling Xie, JinPeng Zhu
Gastric cancer is a prevalent cancer and chemotherapy is a main treatment for patients. Docetaxel is commonly used as a chemotherapeutic drug for gastric cancer patients. With the increasing emergence of docetaxel resistance, exploring the mechanism of chemoresistance may improve prognosis of patients. In this study, we found that overexpressed miR-361-5p suppressed chemoresistance to docetaxel of gastric cancer cells (SGC-7901, MKN-28) by decreasing IC 50 values of docetaxel while increasing cell apoptosis rate, especially in docetaxel resistant SGC-7901 cells...
January 12, 2018: Oncotarget
Ewelina Zielinska, Agata Zauszkiewicz-Pawlak, Michal Wojcik, Iwona Inkielewicz-Stepniak
Pancreatic ductal adenocarcinoma, with the high resistance to chemotherapeutic agents, remains the fourth leading cause of cancer-death in the world. Due to the wide range of biological activity and unique properties, silver nanoparticles (AgNPs) are indicated as agents with potential to overcome barriers involved in chemotherapy failure. Therefore, in our study we decided to assess the ability of AgNPs to kill pancreatic cancer cells, and then to identify the molecular mechanism underlying this effect. Moreover, we evaluated the cytotoxicity of AgNPs against non-tumor cell of the same tissue (hTERT-HPNE cells) for comparison...
January 12, 2018: Oncotarget
Lian Wang, Zhouchun Shang, Yang Zhou, Xinyu Hu, Yihong Chen, Yantao Fan, Xiaoyu Wei, Liang Wu, Qiujuan Liang, Jun Zhang, Zhengliang Gao
Metabolic reprogramming is pivotal to sustain cancer growth and progression. As such dietary restriction therapy represents a promising approach to starve and treat cancers. Nonetheless, tumors are dynamic and heterogeneous populations of cells with metabolic activities modulated by spatial and temporal contexts. Autophagy is a major pathway controlling cell metabolism. It can downregulate cell metabolism, leading to cancer cell quiescence, survival, and chemoresistance. To understand treatment dynamics and provide rationales for better future therapeutic strategies, we investigated whether and how autophagy is involved in the chemo-cytotoxicity and -resistance using two commonly used human glioblastoma (GBM) cell lines U87 and U251 together with primary cancer cells from the GBM patients...
February 12, 2018: Cell Death & Disease
Sajal K Ghosh, Abhishek Ganta, Remco A Spanjaard
BACKGROUND: Chemotherapy and targeted therapies have made important strides in cancer treatment yet they often fail and new therapies are still needed. Here, we employed a phenotypic screen to identify and analyze the mechanism of action of novel small molecules that interfere with critical pathways involved in tumor cell growth, using chemoresistant A375 melanoma cells as a model. METHODS: Cell culture studies were performed in ATCC-recommended media. Compounds, and compound libraries were obtained from Boston University or purchased commercially...
February 8, 2018: Journal of Biomedical Science
Lin Wang, Bing Tang, Heng Han, Dan Mao, Jie Chen, Yun Zeng, Min Xiong
OBJECTIVE: Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) plays a positive regulatory role on cell autophagy through inhibiting PI3K/AKT/mammalian target of rapamycin (mTOR) signaling pathway. miR-155 plays a critical role in osteosarcoma occurrence and chemoresistance. Bioinformatics analysis revealed the targeted binding site between miR-155 and the 3'-UTR (untranslated region) of PTEN mRNA. This study investigated the role of miR-155 in regulating osteosarcoma cell autophagy, chemosensitivity to Adriamycin (ADM), and PTEN-PI3K/AKT/mTOR signaling pathway...
February 7, 2018: Cancer Biotherapy & Radiopharmaceuticals
Santanu Maji, Sanjay Panda, Sabindra K Samal, Omprakash Shriwas, Rachna Rath, Maurizio Pellecchia, Luni Emdad, Swadesh K Das, Paul B Fisher, Rupesh Dash
Cancer is a daunting global problem confronting the world's population. The most frequent therapeutic approaches include surgery, chemotherapy, radiotherapy, and more recently immunotherapy. In the case of chemotherapy, patients ultimately develop resistance to both single and multiple chemotherapeutic agents, which can culminate in metastatic disease which is a major cause of patient death from solid tumors. Chemoresistance, a primary cause of treatment failure, is attributed to multiple factors including decreased drug accumulation, reduced drug-target interactions, increased populations of cancer stem cells, enhanced autophagy activity, and reduced apoptosis in cancer cells...
2018: Advances in Cancer Research
Chung-Ying Tsai, Hsiang-Cheng Chi, Lang-Ming Chi, Huang-Yu Yang, Ming-Ming Tsai, Kam-Fai Lee, Hsiang-Wei Huang, Li-Fang Chou, Ann-Joy Cheng, Chih-Wei Yang, Chia-Siu Wang, Kwang-Huei Lin
Argininosuccinate synthetase 1 (ASS1) is a rate-limited enzyme in arginine biosynthesis. The oncogenic potential of ASS1 in terms of prognosis and cancer metastasis in arginine prototrophic gastric cancer (GC) remains unclear at present. We identify differentially expressed proteins in microdissected GC tumor cells relative to adjacent nontumor epithelia by isobaric mass tag for relative and absolute quantitation proteomics analysis. GC cells with stable expression or depletion of ASS1 were further analyzed to identify downstream molecules...
January 10, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Han Zhang
Autophagy (also known as macroautophagy) is a lysosomal degradation pathway for the clearance of cellular materials, which manifests as an adaptive response to stress stimuli. Over the past decade, numerous studies have linked autophagy with cancer initiation, progression, and chemoresistance. Autophagy defects in normal cells facilitate tumorigenesis; paradoxically, enhanced autophagy allows prolonged survival in cancer cells upon nutrient shortage, low oxygen, or chemotherapies. However, the mechanism underlying the switch from the cytoprotective role of autophagy to autophagic cell death remains incompletely understood...
January 27, 2018: International Journal of Hematology
Xinming Du, Bing Liu, Xuerong Luan, Qing Cui, Leping Li
Chemotherapy is an important treatment modality for gastric cancer, and multidrug resistance (MDR) represents a major obstacle for successful cancer chemotherapy. There is a lack of research on whether microRNA (miR)-30a regulation affects the chemosensitivity of resistant gastric cancer cells, and mechanisms underlying the effects of miR-30a on drug resistance and cell autophagy require further investigation. In the present study, the expression of miR-30a and its effects in cisplatin (CDDP)-resistant human gastric cancer cells were investigated...
January 2018: Experimental and Therapeutic Medicine
Xiang Li, Shichang Deng, Mingliang Liu, Yan Jin, Shuai Zhu, Shijiang Deng, Jingyuan Chen, Chi He, Qi Qin, Chunyou Wang, Gang Zhao
Cancer cells predominantly produce energy at a high rate of glycolysis even in aerobic environment. It is termed as Warburg effect and is necessary for the tumorigenesis. Studies showed pyruvate kinase M2 (PKM2), a key regulator of the Warburg effect, is overexpressed and involved in numerous cancers. However, the expression and function of PKM2 in pancreatic cancer (PC) remain undefined. Our results showed that PKM2 is overexpressed in the PC tissue compared to the peritumoral tissue. Unexpected, the downregulation of PKM2 did not affect the proliferation, invasion, and chemoresistance of PC cells...
January 26, 2018: Cell Death & Disease
Sandra Valle, Laura Martin-Hijano, Sonia Alcalá, Marta Alonso-Nocelo, Bruno Sainz
Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, is the 4th most frequent cause of cancer-related death worldwide, primarily due to the inherent chemoresistant nature and metastatic capacity of this tumor. The latter is believed to be mainly due to the existence of a subpopulation of highly plastic "stem"-like cells within the tumor, known as cancer stem cells (CSCs), which have been shown to have unique metabolic, autophagic, invasive, and chemoresistance properties that allow them to continuously self-renew and escape chemo-therapeutic elimination...
January 26, 2018: Cancers
Ying Xu, Chunying Miao, Chengjuan Jin, Chunping Qiu, Yinuo Li, Xiaomei Sun, Min Gao, Nan Lu, Beihua Kong
The activation of Notch3 is associated with potential progression of ovarian cancer, tumor invasion, metastasis and chemoresistance, which account for poor prognosis of high grade serous ovarian cancer (HGSOC). However, the underlying mechanisms of Notch3 are not yet very clear. Here we show that SUSD2 is one of Notch3-regulating genes and the elevated protein expression of SUSD2 in HGSOC. We also found that its high expression level was significantly correlated with worse overall survival, early recurrence and lymph nodes metastasis...
January 2, 2018: Experimental Cell Research
Junjie Xiong, Dan Wang, Ailin Wei, Nengwen Ke, Yichao Wang, Jie Tang, Sirong He, Weiming Hu, Xubao Liu
Gemcitabine-based chemotherapy is the most common treatment option for pancreatic ductal adenocarcinoma (PDAC). However, it offers little therapeutic value in many cases due to the rapid development of chemoresistance. MicroRNAs (miRNAs) have been found to play pivotal roles in the chemotherapeutic resistance of PDAC. We found that miR-410-3p was significantly down-regulated in human pancreatic cancer xenograft (HPCx) tumor tissues from gemcitabine-treated mice. Low miR-410-3p expression correlated with gemcitabine resistance in HPCx tumors and PDAC cells as well as poor prognosis in PDAC patients...
December 8, 2017: Oncotarget
Yue Cheng, Runwu Ban, Wei Liu, Hongzhi Wang, Shuzhi Li, Zhenfei Yue, Gang Zhu, Yuan Zhuan, Changjuan Wang
Background: Efficacy of chemotherapy for ovarian cancer (OC) is usually affected by various factors,especially the chemoresistance of ovarian cancer cells. Downregulation of miR-409-3p has been found in a variety of tumors. However, the role of miR-409-3p in chemo-resistant OC cells still remains unknown. The aim of this study was to investigate the effect of miR-409-3p on cisplatin-resistant OC cells and to elucidate the mechanism by which enhances cisplatin-sensitivity of OC cells. Methods: Expression of miR-409-3p in OC cells was assessed by qRT-PCR...
January 2, 2018: Oncology Research
Jin Zeng, Wei Liu, Yi-Zeng Fan, Da-Lin He, Lei Li
Rationale: Docetaxel-mediated chemotherapy is the first-line standard approach and has been determined to show a survival advantage for metastatic castration-resistant prostate cancer (mCRPC) patients. However, a substantial proportion of patients eventually becomes refractory due to drug resistance. The detailed mechanisms remain unclear. We have previously reported that Prostate Leucine Zipper (PrLZ), a specific oncogene of prostate cancer (PCa), promotes PCa cell growth at the castration-resistant stage, thus suggesting a vital role of PrLZ in the progression of CRPC...
2018: Theranostics
David Schlütermann, Margaretha A Skowron, Niklas Berleth, Philip Böhler, Jana Deitersen, Fabian Stuhldreier, Nora Wallot-Hieke, Wenxian Wu, Christoph Peter, Michèle J Hoffmann, Günter Niegisch, Björn Stork
BACKGROUND: Cisplatin-based regimens are routinely employed for the treatment of urothelial carcinoma. However, therapeutic success is hampered by the primary presence of or the development of cisplatin resistance. This chemoresistance is executed by multiple cellular pathways. In recent years, the cellular process of autophagy has been identified as a prosurvival pathway of cancer cells. On the one hand, autophagy enables cancer cells to survive conditions of low oxygen or nutrient supply, frequently found in tumors...
December 21, 2017: Urologic Oncology
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