Analysis of the differences in the Expression of mRNAs and miRNAs Asso-ciated with Drug Resistance in Endometrial Cancer Cells Treated with Salinomycin

2020 ◽  
Vol 21 ◽  
Author(s):  
Piotr Januszyk ◽  
Krzysztof Januszyk ◽  
Magdalena Wierzbik-Strońska ◽  
Dariusz Boroń ◽  
Beniamin Grabarek
Keyword(s):  
Drug Resistance ◽  
Endometrial Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Cancer Cell Line ◽  
Control Culture ◽  
New Drugs ◽  
Cancer Drug ◽  
Cancer Drug Resistance ◽  
Expression Of Genes

Background: It is important to understand the molecular mechanisms involved in cancer drug resistance and to study the activity of new drugs, e.g. salinomycin. Objective: The purpose of the study was to analyze changes in the expression of genes associated with drug resistance in the Ishikawa endometrial cancer cell line when treated with salinomycin. In addition, changes in the level of miRNA potentially regulating these mRNAs were evaluated. Results: The following was observed about the number of mRNAs differentiating the cell culture exposed to the drug compared to a control culture: H-12 vs C - 9 mRNAs, H_24 vs C – 6 mRNAs, H_48 vs C - 1 mRNA. It was noted that 4 of the 9 differentiating mRNAs were characteristic for 12 hours of exposure to the salinomycin and they correspond to the following genes: TUFT1, ABCB1, MTMR11, MX2. After 24 hours, 2 mRNAs were characteristic for this time of incubation cells with salinomycin: TUFT1, MYD88 and after 48 hours, SLC30A5 could also be observed. The highest differences in expression were indicated for TUFT1, MTMR11, SLC30A5. The highest influence probability was determined between TUFT1 and hsamiR-3188 (FC + 2.48), MTMR11and has-miR-16 (FC -1.74), and between SLC30A5 and hsa-miR-30d (FC -2.01). Materials and Methods: Endometrial cancer cells were treated with 1 µM of salinomycin for 12, 24 and 48 hour periods. Untreated cells were a control culture. The molecular analysis consists of mRNA and miRNA microarray analysis and the RTqPCR technique. Conclusions: Salinomycin induces changes in the activity of mRNA and miRNA participating in drug resistance, however the observed changes in character are an expected result of anti-cancer treatment.

Current Advances and Outlook in Gastric Cancer Chemoresistance: A Review

2021 ◽  
Vol 16 ◽  
Author(s):  
Sheng-Xiong Zhang ◽  
Wei Liu ◽  
Bo Ai ◽  
Ling-Ling Sun ◽  
Zhe-Sheng Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Natural Products ◽  
Chemotherapy Resistance ◽  
Underlying Mechanism ◽  
Primary Treatment ◽  
New Drugs ◽  
Cancer Drug ◽  
Cancer Drug Resistance ◽  
Cancer Pharmacology

Background: Surgical resection of the lesion is the standard primary treatment of gastric cancer. Unfortunately, most patients are already in the advanced stage of the disease when they are diagnosed with gastric cancer. Alternative therapies, such as radiation therapy and chemotherapy, can achieve only very limited benefits. The emergence of cancer drug resistance has always been the major obstacle to the cure of tumors. The main goal of modern cancer pharmacology is to determine the underlying mechanism of anticancer drugs. Objective: Here, we mainly review the latest research results related to the mechanism of chemotherapy resistance in gastric cancer, the application of natural products in overcoming the chemotherapy resistance of gastric cancer, and the new strategies currently being developed to treat tumors based on immunotherapy and gene therapy. Conclusion: The emergence of cancer drug resistance is the main obstacle in achieving alleviation and final cure for gastric cancer. Mixed therapies are considered to be a possible way to overcome chemoresistance. Natural products are the main resource for discovering new drugs specific for treating chemoresistance, and further research is needed to clarify the mechanism of natural product activity in patients. 

scholarly journals The role of photodynamic therapy in overcoming cancer drug resistance

2015 ◽  
Vol 14 (8) ◽  
pp. 1476-1491 ◽  
Author(s):  
Bryan Q. Spring ◽  
Imran Rizvi ◽  
Nan Xu ◽  
Tayyaba Hasan
Keyword(s):  
Drug Resistance ◽  
Photodynamic Therapy ◽  
Cancer Cells ◽  
Cancer Drug ◽  
Cancer Drug Resistance

This perspective highlights unique mechanisms of photodynamic therapy (PDT) that can be utilized to overcome classical drug resistance and re-sensitize resistant cancer cells for standard therapies.

Evaluation of Variances in VEGF-A-D and VEGFR-1-3 Expression in the Ishikawa Endometrial Cancer Cell Line Treated with Salinomycin and An-ti-Angiogenic/Lymphangiogenic Effect

2020 ◽  
Vol 21 ◽  
Author(s):  
Piotr Kras ◽  
Karol Talkowski ◽  
Beniamin Oskar Grabarek ◽  
Nina Dziobek ◽  
Dariusz Boroń ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Cells ◽  
Expression Pattern ◽  
Lymphatic Vessels ◽  
Cancer Cell Line ◽  
Control Culture ◽  
Significant Difference ◽  
Correct Pattern ◽  
The Difference ◽  
Endothelial Growth Factor

Background: In cancer, an excessive and uncontrolled process of creating new blood and lymphatic vessels that play a key role in the metastasis process can be observed. The vascular endothelial growth factor (VEGF-A,-B,-C,-D) family together with their specific receptors (VEGFR-1,-2,-3) plays a key role in these processes, therefore it would be reasonable to determine the correct pattern of their expression. Objective: The study aimed to assess the use of salinomycin as an anti-angiogenic and anti-lymphangiogenic drug during endometrial cancer by examining changes in the expression pattern of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGFR-1, VEGFR-2, VEGFR-3 depending on the treatment period of the Ishikawa endometrial cancer cells with salinomycin in comparison to the control culture. Materials and Methods: To determine how influential salinomycin was on the expression of both mRNAs, 1 µM of the drug was added to the cell culture and then it was cultured all together for 12,24 and 48 hour periods. The cells that made up the control culture were not treated with salinomycin. To determine the changes in the expression profile of the selected genes we used the microarray, techniques: RTqPCR and ELISA (p<0.05). Results: For all isoforms of VEGF-A-D as well as receptors of VEGFR-1-3, a decrease in expression under the influence of salinomycin was noted. For VEGF-A and VEGFR-1, the difference in the expression between the culture treated with salinomycin in comparison to the control was statistically significant (p=0.0004). In turn for VEGF-B, the difference between the culture exposed for 24 hours in comparison to the control (p=0.00000) as well as the comparison between H48 vs C (p=0.00000) was statistically significant. In reference to VEGF-C, VEGFR-2, VEGFR-3 the statistical analysis showed the significant difference in expression between the culture incubated with the drug for 12,24 and 48 hours in comparison to the control as well as between the selected times. For all of these comparisons, p=0.00000 was utilized. Conclusions: Salinomycin changes the expression pattern of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGFR-1, VEGFR-2, and VEGFR-3 in endometrial cancer cells. The obtained results suggest that salinomycin might exert the effect via VEGF signaling pathways.

Repurposing Disulfiram as An Anti-Cancer Agent: Updated Review on Literature and Patents

2019 ◽  
Vol 14 (2) ◽  
pp. 113-132 ◽  
Author(s):  
Elmira Ekinci ◽  
Sagar Rohondia ◽  
Raheel Khan ◽  
Qingping P. Dou
Keyword(s):  
Drug Resistance ◽  
Superoxide Dismutase ◽  
Dna Methyltransferase ◽  
Molecular Mechanisms ◽  
Chronic Alcoholism ◽  
New Drugs ◽  
Mitogen Activated Protein Kinase ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Anti Cancer

Background:Despite years of success of most anti-cancer drugs, one of the major clinical problems is inherent and acquired resistance to these drugs. Overcoming the drug resistance or developing new drugs would offer promising strategies in cancer treatment. Disulfiram, a drug currently used in the treatment of chronic alcoholism, has been found to have anti-cancer activity.Objective:To summarize the anti-cancer effects of Disulfiram through a thorough patent review.Methods:This article reviews molecular mechanisms and recent patents of Disulfiram in cancer therapy.Results:Several anti-cancer mechanisms of Disulfiram have been proposed, including triggering oxidative stress by the generation of reactive oxygen species, inhibition of the superoxide dismutase activity, suppression of the ubiquitin-proteasome system, and activation of the mitogen-activated protein kinase pathway. In addition, Disulfiram can reverse the resistance to chemotherapeutic drugs by inhibiting the P-glycoprotein multidrug efflux pump and suppressing the activation of NF-kB, both of which play an important role in the development of drug resistance. Furthermore, Disulfiram has been found to reduce angiogenesis because of its metal chelating properties as well as its ability to inactivate Cu/Zn superoxide dismutase and matrix metalloproteinases. Disulfiram has also been shown to inhibit the proteasomes, DNA topoisomerases, DNA methyltransferase, glutathione S-transferase P1, and O6- methylguanine DNA methyltransferase, a DNA repair protein highly expressed in brain tumors. The patents described in this review demonstrate that Disulfiram is useful as an anti-cancer drug.Conclusion:For years the FDA-approved, well-tolerated, inexpensive, orally-administered drug Disulfiram was used in the treatment of chronic alcoholism, but it has recently demonstrated anti-cancer effects in a range of solid and hematological malignancies. Its combination with copper at clinically relevant concentrations might overcome the resistance of many anti-cancer drugs in vitro, in vivo, and in patients.

scholarly journals Sensitization of Drug Resistant Cancer Cells: A Matter of Combination Therapy

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 483 ◽  
Author(s):  
Meghan Leary ◽  
Sarah Heerboth ◽  
Karolina Lapinska ◽  
Sibaji Sarkar
Keyword(s):  
Drug Resistance ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Progenitor Cells ◽  
Rational Design ◽  
Cancer Drug ◽  
Drug Resistant ◽  
Combination Therapies ◽  
Cancer Drug Resistance ◽  
Rational Development

Cancer drug resistance is an enormous problem. It is responsible for most relapses in cancer patients following apparent remission after successful therapy. Understanding cancer relapse requires an understanding of the processes underlying cancer drug resistance. This article discusses the causes of cancer drug resistance, the current combination therapies, and the problems with the combination therapies. The rational design of combination therapy is warranted to improve the efficacy. These processes must be addressed by finding ways to sensitize the drug-resistant cancers cells to chemotherapy, and to prevent formation of drug resistant cancer cells. It is also necessary to prevent the formation of cancer progenitor cells by epigenetic mechanisms, as cancer progenitor cells are insensitive to standard therapies. In this article, we emphasize the role for the rational development of combination therapy, including epigenetic drugs, in achieving these goals.

Clinical relevance of the molecular mechanisms of resistance to anti-cancer drugs

1999 ◽  
Vol 1 (15) ◽  
pp. 1-21 ◽  
Author(s):  
Robert Brown ◽  
Matthew Links
Keyword(s):  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Positive Response ◽  
Cancer Drug ◽  
Clinical Relapse ◽  
Cancer Drugs ◽  
Cancer Drug Resistance ◽  
Anti Cancer ◽  
Or Genes ◽  
Clinical Drug

Resistance to anti-cancer drugs (drug resistance) can be defined in the laboratory by the amount of anti-cancer drug that is required to produce a given level of cell death (drug response). Clinical drug resistance can be defined either as a lack of reduction of the size of a tumour following chemotherapy or as the occurrence of clinical relapse after an initial ‘positive’ response to anti-tumour treatment. Many studies of tumour samples do not directly measure drug resistance in the laboratory (because it is difficult to perform functional assays on tumour tissue); instead, key proteins or genes that are involved in particular mechanisms of drug resistance have been proposed as ‘markers’ of drug resistance. In this review, we have focused on the problems that can arise when attempts are made to relate the relevance of laboratory-identified molecular mechanisms of drug resistance to anti-cancer drug resistance that occurs in patients.

scholarly journals Modeling adaptive drug resistance of colorectal cancer and therapeutic interventions with tumor spheroids

2021 ◽  
pp. 153537022110141
Author(s):  
Astha Lamichhane ◽  
Pradip Shahi Thakuri ◽  
Pouria Rafsanjani Nejad ◽  
Hossein Tavana
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Tumor Biology ◽  
Three Dimensional ◽  
Therapeutic Interventions ◽  
Cancer Drug ◽  
Tumor Spheroids ◽  
Major Barrier ◽  
Cancer Drug Discovery ◽  
Cancer Drug Resistance

Drug resistance is a major barrier against successful treatments of cancer patients. Various intrinsic mechanisms and adaptive responses of tumor cells to cancer drugs often lead to failure of treatments and tumor relapse. Understanding mechanisms of cancer drug resistance is critical to develop effective treatments with sustained anti-tumor effects. Three-dimensional cultures of cancer cells known as spheroids present a biologically relevant model of avascular tumors and have been increasingly incorporated in tumor biology and cancer drug discovery studies. In this review, we discuss several recent studies from our group that utilized colorectal tumor spheroids to investigate responses of cancer cells to cytotoxic and molecularly targeted drugs and uncover mechanisms of drug resistance. We highlight our findings from both short-term, one-time treatments and long-term, cyclic treatments of tumor spheroids and discuss mechanisms of adaptation of cancer cells to the treatments. Guided by mechanisms of resistance, we demonstrate the feasibility of designing specific drug combinations to effectively block growth and resistance of cancer cells in spheroid cultures. Finally, we conclude with our perspectives on the utility of three-dimensional tumor models and their shortcomings and advantages for phenotypic and mechanistic studies of cancer drug resistance.

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