scholarly journals Research Progress of MicroRNA in Chemotherapy Resistance of Osteosarcoma

2021 ◽  
Vol 20 ◽  
pp. 153303382110342
Author(s):  
Zhaopeng Tang ◽  
Yubao Lu ◽  
Yutong Chen ◽  
Jiarui Zhang ◽  
Zhijun Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Effective Treatment ◽  
Cancer Cells ◽  
Metabolic Response ◽  
Chemotherapy Resistance ◽  
Chemotherapeutic Agents ◽  
Medical Community ◽  
Research Progress ◽  
Community Studies ◽  
Chemotherapy Drugs

Osteosarcoma (OS) is a malignant tumor prevalent in adolescents; however, a clinically effective treatment for this malignancy is lacking. The lack of effective treatment methods and factors, such as recurrence and drug resistance, further dampen the prospect of clinically treating OS. In recent years, small molecule microRNAs (miRNAs) with a length of approximately 20-24 nucleotides have gradually attracted the attention of the medical community. Studies have found that miRNAs can regulate the cell cycle, apoptosis, cell proliferation, and cell proliferation. The metabolic response of cancer cells, invasion and metastasis of cancer cells, and angiogenesis play an important role in the process of tumorigenesis. miRNAs regulate gene expression by regulating mRNA expression after transcription. A large amount of data from many studies indicate that they have diagnostic and prognostic biomarker effects in OS and are involved in regulating the metabolism of cancer cells and resistance or sensitivity to chemotherapy drugs. Chemotherapy resistance is one of the most critical problems in clinically treating OS. A large number of basic studies and systematic summaries are required to provide a theoretical basis for elucidating the mechanism and drug development of chemotherapeutic agents. Therefore, this article discusses the role of miRNAs in OS resistance. Herein, the related research progress of the studies is reviewed to provide more useful information for the development of effective therapy.

scholarly journals Metabolic Reprogramming of Chemoresistant Cancer Cells and the Potential Significance of Metabolic Regulation in the Reversal of Cancer Chemoresistance

Metabolites ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 289 ◽  
Author(s):  
Xun Chen ◽  
Shangwu Chen ◽  
Dongsheng Yu
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Metabolic Regulation ◽  
Metabolic Response ◽  
Pentose Phosphate ◽  
Metabolic Reprogramming ◽  
Acid Oxidation ◽  
Drug Resistant ◽  
Chemotherapy Drugs

Metabolic reprogramming is one of the hallmarks of tumors. Alterations of cellular metabolism not only contribute to tumor development, but also mediate the resistance of tumor cells to antitumor drugs. The metabolic response of tumor cells to various chemotherapy drugs can be analyzed by metabolomics. Although cancer cells have experienced metabolic reprogramming, the metabolism of drug resistant cancer cells has been further modified. Metabolic adaptations of drug resistant cells to chemotherapeutics involve redox, lipid metabolism, bioenergetics, glycolysis, polyamine synthesis and so on. The proposed metabolic mechanisms of drug resistance include the increase of glucose and glutamine demand, active pathways of glutaminolysis and glycolysis, promotion of NADPH from the pentose phosphate pathway, adaptive mitochondrial reprogramming, activation of fatty acid oxidation, and up-regulation of ornithine decarboxylase for polyamine production. Several genes are associated with metabolic reprogramming and drug resistance. Intervening regulatory points described above or targeting key genes in several important metabolic pathways may restore cell sensitivity to chemotherapy. This paper reviews the metabolic changes of tumor cells during the development of chemoresistance and discusses the potential of reversing chemoresistance by metabolic regulation.

scholarly journals Cisplatin Synergistically Enhances Antitumor Potency of Conditionally Replicating Adenovirus via p53 Dependent or Independent Pathways in Human Lung Carcinoma

2019 ◽  
Vol 20 (5) ◽  
pp. 1125 ◽  
Author(s):  
Sakhawat Ali ◽  
Muhammad Tahir ◽  
Aamir Khan ◽  
Xue Chen ◽  
Ma Ling ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Combined Treatment ◽  
Acquired Resistance ◽  
Chemotherapy Resistance ◽  
Chemotherapeutic Agents ◽  
Lung Cancer Cells ◽  
Advanced Lung Cancer ◽  
Mesenchymal Transition ◽  
Conditionally Replicating Adenovirus

Cisplatin is ranked as one of the most powerful and commonly prescribed anti-tumor chemotherapeutic agents which improve survival in many solid tumors including non-small cell lung cancer. However, the treatment of advanced lung cancer is restricted due to chemotherapy resistance. Here, we developed and investigated survivin promoter regulating conditionally replicating adenovirus (CRAd) for its anti-tumor potential alone or in combination with cisplatin in two lung cancer cells, H23, H2126, and their resistant cells, H23/CPR, H2126/CPR. To measure the expression of genes which regulate resistance, adenoviral transduction, metastasis, and apoptosis in cancer cells, RT-PCR and Western blotting were performed. The anti-tumor efficacy of the treatments was evaluated through flow cytometry, MTT and transwell assays. This study demonstrated that co-treatment with cisplatin and CRAd exerts synergistic anti-tumor effects on chemotherapy sensitive lung cancer cells and monotherapy of CRAd could be a practical approach to deal with chemotherapy resistance. Combined treatment induced stronger apoptosis by suppressing the anti-apoptotic molecule Bcl-2, and reversed epithelial to mesenchymal transition. In conclusion, cisplatin synergistically increased the tumor-killing of CRAd by (1) increasing CRAd transduction via enhanced CAR expression and (2) increasing p53 dependent or independent apoptosis of lung cancer cell lines. Also, CRAd alone proved to be a very efficient anti-tumor agent in cancer cells resistant to cisplatin owing to upregulated CAR levels. In an exciting outcome, we have revealed novel therapeutic opportunities to exploit intrinsic and acquired resistance to enhance the therapeutic index of anti-tumor treatment in lung cancer.

scholarly journals Transient Receptor Potential Cation Channels in Cancer Therapy

2019 ◽  
Vol 7 (12) ◽  
pp. 108 ◽  
Author(s):  
Giorgio Santoni ◽  
Federica Maggi ◽  
Maria Beatrice Morelli ◽  
Matteo Santoni ◽  
Oliviero Marinelli
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Cancer Cells ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Chemotherapeutic Agents ◽  
Migration And Invasion ◽  
Transient Receptor

In mammals, the transient receptor potential (TRP) channels family consists of six different families, namely TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPML (mucolipin), TRPP (polycystin), and TRPA (ankyrin), that are strictly connected with cancer cell proliferation, differentiation, cell death, angiogenesis, migration, and invasion. Changes in TRP channels’ expression and function have been found to regulate cell proliferation and resistance or sensitivity of cancer cells to apoptotic-induced cell death, resulting in cancer-promoting effects or resistance to chemotherapy treatments. This review summarizes the data reported so far on the effect of targeting TRP channels in different types of cancer by using multiple TRP-specific agonists, antagonists alone, or in combination with classic chemotherapeutic agents, microRNA specifically targeting the TRP channels, and so forth, and the in vitro and in vivo feasibility evaluated in experimental models and in cancer patients. Considerable efforts have been made to fight cancer cells, and therapies targeting TRP channels seem to be the most promising strategy. However, more in-depth investigations are required to completely understand the role of TRP channels in cancer in order to design new, more specific, and valuable pharmacological tools.

scholarly journals Exosomal Micro RNA-107 Reverses Chemotherapeutic Drug Resistance of Gastric Cancer Cells Through HMGA2/mTOR/P-gp Pathway

2021 ◽  
Author(s):  
Lu Jiang ◽  
Yan Zhang ◽  
Linghui Guo ◽  
Chaoyang Liu ◽  
Weihong Ren
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Chemotherapeutic Agents ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Gastric Cancer Cells ◽  
Chemotherapy Drug ◽  
Chemotherapy Drugs

Abstract Background: RNA cargo in exosomes，especially microRNAs (miRNAs), play an important role in the chemotherapy drug resistance of human cancers. However, the role and mechanism of exosomal miR-107 on multidrug resistance of gastric cancer cells was still not clear. In this study, we sought to explore whether exosomal miR-107 could reverse theresistance of gastric cancer cells to the chemotherapy drugs. Methods: We extracted exosomes from sensitive (SGC-7901, MGC-803) and resistant (SGC-7901/5-FU) gastric cancer cells by ultracentrifugation and the isolated exosomes were identified using transmission electron microscopy (TEM) and dynamic light scattering analysis (DLS). The expression of miR-107 and high mobility group A2 (HMGA2) were detected by real-time quantitative PCR (RT-qPCR). MTT assay was used to investigate the effect of exosomes on gastric cancer cells growth in vitro. The uptake of exosomes by recipient cells were observed using a fluorescence microscope. The predicted target relationship between miR-107 and HMGA2 was verified by gauss-luciferase reporter assay. The expression of HMGA2, p-mTOR/mTOR, P-gp and other exosomal indicated marker proteins were detected by western blot. Results: Our results indicated that the isolated exosomes were demostrated typically cup-like lipid bilayer membrans structure. SGC-7901/5-FU cells were cross-resistant to chemotherapy drug cisplatin (DDP), and the sensitive cells-secreted exosomes drastically reversed the resistance of the resistant gastric cells to the chemotherapeutic drugs,which was verificated by exosomal inhibitor GW4896. Mechanistically, the reversal effect were mainly mediated by exosome-secreted miR-107 through downregulating the expression of targert molecular HMGA2, and inhibiting HMGA2/mTOR/P-gp pathway, which were proofed by luciferase reporter assay and rescue assay. Conclusions: These findings demonstrated that exosome-transmitted miR-107 significantly enhanced the sensitivity of resistant gastric cancer cells to chemotherapeutic agents by mediating the HMGA2/mTOR/P-gp axis and appling exosomal miR-107 may be a novel target in gastric cancers treatment.

Research Progress of Axl Inhibitors

2019 ◽  
Vol 19 (15) ◽  
pp. 1338-1349 ◽  
Author(s):  
Zhi-Gang Sun ◽  
Jian-Hua Liu ◽  
Jin-Mai Zhang ◽  
Yong Qian
Keyword(s):  
Skeletal Muscle ◽  
Signal Transduction ◽  
Cell Proliferation ◽  
Drug Resistance ◽  
Receptor Tyrosine Kinase ◽  
Chemotherapy Resistance ◽  
Research Progress ◽  
Invasion And Metastasis ◽  
Over Expression ◽  
Pancreatic Cancers

Axl, a Receptor Tyrosine Kinase (RTK) belonging to the TAM (Axl, Mer, Tyro3) family, participates in many signal transduction cascades after mostly being stimulated by Growth arrestspecific 6(Gas6). Axl is widely expressed in many organs, such as macrophages, endothelial cells, heart, liver and skeletal muscle. Over-expression and activation of Axl are associated with promoting chemotherapy resistance, cell proliferation, invasion and metastasis in many human cancers, such as breast, lung, and pancreatic cancers. Therefore, the research and development of Axl inhibitors is of great significance to strengthen the means of cancer treatment, especially to solve the problem of drug resistance. Axl inhibitors have attracted more and more researchers' attention in recent years. This review discusses the research progress of Axl inhibitors in recent years.

scholarly journals Molecularly targeting the PI3K-Akt-mTOR pathway can sensitize cancer cells to radiotherapy and chemotherapy

2014 ◽  
Vol 19 (2) ◽  
Author(s):  
Ziwen Wang ◽  
Yujung Huang ◽  
Jiqiang Zhang
Keyword(s):  
Dna Damage ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Chemotherapeutic Agents ◽  
Cell Cycle Checkpoint ◽  
Mtor Signaling ◽  
Ras Signaling ◽  
Chemotherapy Drugs ◽  
Cycle Checkpoint

AbstractRadiotherapy and chemotherapeutic agents that damage DNA are the current major non-surgical means of treating cancer. However, many patients develop resistances to chemotherapy drugs in their later lives. The PI3K and Ras signaling pathways are deregulated in most cancers, so molecularly targeting PI3K-Akt or Ras-MAPK signaling sensitizes many cancer types to radiotherapy and chemotherapy, but the underlying molecular mechanisms have yet to be determined. During the multi-step processes of tumorigenesis, cancer cells gain the capability to disrupt the cell cycle checkpoint and increase the activity of CDK4/6 by disrupting the PI3K, Ras, p53, and Rb signaling circuits. Recent advances have demonstrated that PI3K-Akt-mTOR signaling controls FANCD2 and ribonucleotide reductase (RNR). FANCD2 plays an important role in the resistance of cells to DNA damage agents and the activation of DNA damage checkpoints, while RNR is critical for the completion of DNA replication and repair in response to DNA damage and replication stress. Regulation of FANCD2 and RNR suggests that cancer cells depend on PI3K-Akt-mTOR signaling for survival in response to DNA damage, indicating that the PI3K-AktmTOR pathway promotes resistance to chemotherapy and radiotherapy by enhancing DNA damage repair.

scholarly journals Cinobufagin Enhances the Sensitivity of Cisplatin-Resistant Lung Cancer Cells to Chemotherapy by Inhibiting the PI3K/AKT and MAPK/ERK Pathways

2021 ◽  
Author(s):  
Guangxin Zhang ◽  
Xueshibojie Liu ◽  
Yicun Wang ◽  
Chengyan Jin ◽  
Zhengyang Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Chemotherapy Resistance ◽  
Lung Cancer Cells ◽  
Cell Counting ◽  
Pcr Analysis ◽  
Tunel Staining ◽  
Chemotherapy Drugs

Abstract Background: Lung cancer patients always develop serious chemotherapy resistance after long-term use of cisplatin (DDP) treatment. It has been demonstrated that combination of DDP with other chemotherapy drugs may significantly reduce drug resistance. Cinobufagin (CB) showed potent anti-tumor effect against lung cancer. However, the relevance of CB and DDP resistance in lung cancer remains unclear. This article will study the effects of CB on reversing lung cell resistance in vitro and in vivo. Materials and Methods: The cell viability was evaluated using the Cell Counting Kit 8 (CCK8) assay. The apoptosis was detected by flow cytometry analysis and TUNEL staining. The invasiveness was detected by Invasion assay. The mRNA and protein of apoptosis-related proteins, P-AKT, P-PI3K, P-MEK1/2, P-ERK1/2 and MRP1 were estimated by qRT-PCR analysis and western blot analysis, respectively. In vivo antitumor activities were investigated by subcutaneous xenograft assay. Results: The present study firstly demonstrated that the sensitivity of DDP in DDP-resistant A549 (A549/DDP) cells was enhanced when treatment with CB. Moreover, CB combined with DDP significantly weakened the proliferation and increased apoptosis of A549/DDP cells. In addition, the expression level of Bcl-2 was increased, whereas Bax and Caspase-3 were activated when A549/DDP cells were treated with both drugs. Moreover, after treatment with IGF1 (activator of PI3K/AKT) or PMA (activator of MAPK/ERK) and mixed drugs (CB+DDP), the expressions of P-AKT, P-PI3K, P-MEK1/2 and P-ERK1/2 were increased. Finally, the results of in vivo experiments showed that the combination of DDP and CB significantly reduced the growth of tumors derived from A549/DDP cells. Conclusions: In summary, the results of this study indicate that the combination of CB and DDP can be considered an effective strategy to increase the sensitivity of DDP-resistant lung cancer cells to DDP by inhibiting the PI3K/AKT and MAPK/ERK pathways.

scholarly journals Targeting the Multidrug Transporter Ptch1 Potentiates Chemotherapy Efficiency

Cells ◽  
2018 ◽  
Vol 7 (8) ◽  
pp. 107 ◽  
Author(s):  
Anida Hasanovic ◽  
Isabelle Mus-Veteau
Keyword(s):  
Cancer Cells ◽  
Abc Transporters ◽  
Adrenocortical Carcinoma ◽  
Efflux Pump ◽  
Therapeutic Option ◽  
Chemotherapy Resistance ◽  
Chemotherapeutic Agents ◽  
Multidrug Transporter ◽  
Drug Efflux

One of the crucial challenges in the clinical management of cancer is resistance to chemotherapeutics. Multidrug resistance (MDR) has been intensively studied, and one of the most prominent mechanisms underlying MDR is overexpression of adenosine triphosphate (ATP)-binding cassette (ABC) transporters. Despite research efforts to develop compounds that inhibit the efflux activity of ABC transporters and thereby increase classical chemotherapy efficacy, to date, the Food and Drug Administration (FDA) has not approved the use of any ABC transporter inhibitors due to toxicity issues. Hedgehog signaling is aberrantly activated in many cancers, and has been shown to be involved in chemotherapy resistance. Recent studies showed that the Hedgehog receptor Ptch1, which is over-expressed in many recurrent and metastatic cancers, is a multidrug transporter and it contributes to the efflux of chemotherapeutic agents such as doxorubicin, and to chemotherapy resistance. Remarkably, Ptch1 uses the proton motive force to efflux drugs, in contrast to ABC transporters, which use ATP hydrolysis. Indeed, the “reversed pH gradient” that characterizes cancer cells, allows Ptch1 to function as an efflux pump specifically in cancer cells. This makes Ptch1 a particularly attractive therapeutic target for cancers expressing Ptch1, such as lung, breast, prostate, ovary, colon, brain, adrenocortical carcinoma, and melanoma. Screening of chemical libraries have identified several molecules that are able to enhance the cytotoxic effect of different chemotherapeutic agents by inhibiting Ptch1 drug efflux activity in different cancer cell lines that endogenously over-express Ptch1. In vivo proof of concept has been performed in mice where combining one of these compounds with doxorubicin prevented the development of xenografted adrenocortical carcinoma tumors more efficiently than doxorubicin alone, and without obvious undesirable side effects. Therefore, the use of a Ptch1 drug efflux inhibitor in combination with classical or targeted therapy could be a promising therapeutic option for Ptch1-expressing cancers.

scholarly journals Gadolinium oxide nanoparticles enhance the cytotoxicity of chemotherapeutic drugs by blocking autophagic flux in cancer cells

2019 ◽  
Author(s):  
Tianyu Zhang ◽  
Cheng Zhong ◽  
Zhixiong Xie
Keyword(s):  
Cancer Cells ◽  
Chemotherapy Resistance ◽  
Gadolinium Oxide ◽  
Oxide Nanoparticles ◽  
Autophagic Flux ◽  
Dependent Manner ◽  
Chemotherapy Drugs ◽  
Cancer Diagnosis And Therapy ◽  
Dose Dependent ◽  
Gadolinium Oxide Nanoparticles

Abstract During chemotherapy, drugs can damage cancer cells’ DNA and cytomembrane structure, and then induce cell death. However, autophagy can increase the chemotherapy resistance of cancer cells, reducing the effect of chemotherapy. We found that gadolinium oxide nanoparticles (Gd2O3 NPs), which have great potential for use as a contrast agent in magnetic resonance imaging, could block the late stage of autophagic flux in a dose-dependent manner and then cause autophagosome accumulation in HeLa cells. When co-treated with 8 μg/mL Gd2O3 NPs and 5 μg/mL cisplatin, the number of dead cancer cells increased by about 20% compared with cisplatin alone. We observed the same phenomenon in cisplatin-resistant COC1/DDP cells. Thus, Gd2O3 NPs have significant potential for use in both cancer diagnosis and therapy.

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