International Journal of Molecular and Cellular Medicine最新文献_第5页

Losartan as a Reproposing Therapeutic Agent in Acute Respiratory Distress Syndrome: Modulating Inflammatory Responses and Cytokine Production. 洛沙坦作为急性呼吸窘迫综合征的替代治疗药物：调节炎症反应和细胞因子的产生。

IF 1.5

International Journal of Molecular and Cellular Medicine Pub Date : 2024-01-01 DOI: 10.22088/IJMCM.BUMS.13.2.120

Khate Sripratak, Phumin Chamsodsai, Jeeraprapa Siriwaseree, Kiattawee Choowongkomon, Lueacha Tabtimmai

{"title":"Losartan as a Reproposing Therapeutic Agent in Acute Respiratory Distress Syndrome: Modulating Inflammatory Responses and Cytokine Production.","authors":"Khate Sripratak, Phumin Chamsodsai, Jeeraprapa Siriwaseree, Kiattawee Choowongkomon, Lueacha Tabtimmai","doi":"10.22088/IJMCM.BUMS.13.2.120","DOIUrl":"10.22088/IJMCM.BUMS.13.2.120","url":null,"abstract":"Seeking a new drug has become a significant milestone in drug discovery. However, it might not be immediately used in urgent situations or during a pandemic. Acute Respiratory Distress Syndrome (ARDS) contributes to mild-to-severe symptoms in patients due to cytokine storms, leading to morbidity and mortality. Hypertension is recognized as an independent risk factor for the severity of ARDS regarding to both ACE Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs) treatment, although the precise mechanism remains unclear. In this study, murine macrophage cell lines (RAW264.7) and alveolar epithelial type II-like cell lines (A549) were utilized to investigate the effect of Losartan (LOS). LOS attenuated nitric oxide production in a dose-dependent manner and collectively reduced intracellular reactive oxygen species (ROS) compared to Diclofenac under LPS-stimulation conditions. For ADRS-mimicking conditions, LPS-induced inflammatory A549 cells were performed to monitor the effect of LOS. The results showed that LOS exhibited a protective effect by increasing cell viability and decreasing intracellular ROS levels. Notably, a high dose of LOS increased intracellular ROS levels. Moreover, LOS treatment downregulated NF-kappaB activation and AT1R at the protein level. Correspondingly, proinflammatory mediator cytokines (TNF-alpha and IL-8) were downregulated, but not IL-6, during LOS treatment. Hence, LOS may provide substantial benefits to ARDS patients by modulating proinflammatory cytokine production through AT1R downregulation and NF-kappaB inactivation. The mechanistic insight into LOS's anti-inflammatory effect holds promise for reducing mortality rates among ARDS patients.","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"13 2","pages":"120-132"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Review of the Interaction between miRNAs and Ebola Virus. 综述 miRNA 与埃博拉病毒之间的相互作用。

IF 1.5

International Journal of Molecular and Cellular Medicine Pub Date : 2024-01-01 DOI: 10.22088/IJMCM.BUMS.13.2.210

Ehsan Kakavandi, Jila Yavarian, Mahdieh Farzanehpour, Mohammad Shayestehpour

引用次数: 0

Cardiac Glycoside Oleandrin Suppresses EMT Ability in Endometrial Carcinoma Cells. 强心苷齐墩果素可抑制子宫内膜癌细胞的 EMT 能力

International Journal of Molecular and Cellular Medicine Pub Date : 2023-01-01 DOI: 10.22088/IJMCM.BUMS.12.3.220

Fatma Secer Celik, Canan Eroglu Gunes, Ercan Kurar

{"title":"Cardiac Glycoside Oleandrin Suppresses EMT Ability in Endometrial Carcinoma Cells.","authors":"Fatma Secer Celik, Canan Eroglu Gunes, Ercan Kurar","doi":"10.22088/IJMCM.BUMS.12.3.220","DOIUrl":"10.22088/IJMCM.BUMS.12.3.220","url":null,"abstract":"Endometrial carcinoma is one of the most common types of cancer among women. The progression of cancer occurs via the Epithelial- Mesenchymal Transition (EMT) pathway. Cells lose their epithelial properties and become mobile. For this reason, the EMT process is one of the most important step to be targeted in cancer treatment. Oleandrin is a cardiac glycoside and its use is limited due to its narrow therapeutic index. In this study, we aimed to evaluate effects of lower level Oleandrin doses on EMT process in endometrial carcinoma. Oleandrin was administrated to Ishikawa endometrial adenocarcinoma cells at different doses and times. IC50 dose was determined by XTT proliferation test. Expression analysis of EMT-related genes was then performed by qRT-PCR. Invasion and colony formation abilities of cells were examined microscopically. Finally, the migration analysis of cancer cells was determined by the Wound Healing Assay. The IC50 dose of Oleandrin applied to Ishikawa cells was determined as 75.3 nM at the 48 h. According to qRT-PCR analysis, expression levels of ZEB1, FN1, ITGB1, VIM, SMAD2, SNAI1, SNAI2, SNAI3, and TGFB3 genes significantly decreased, but TIMP2, TIMP3, ITGAV and GSK3B genes significantly increased. In addition, Oleandrin significantly reduced colony formation and invasion of Ishikawa cells. According to the Wound Healing analysis, the migratory abilities of the Oleandrin-treated cells were reduced compared to the control. Low dose Oleandrin suppresses the EMT pathway in Ishikawa cells. It has been shown that Oleandrin significantly suppresses the cell's colony formation, invasion and migration ability both in gene expression analyzes and microscopically.","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"12 3","pages":"220-228"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of hsa-piR-32877 Suppression with Antisense LNA GapmeRs on the Proliferation and Apoptosis of Human Acute Myeloid Leukemia Cells. 反义LNA-GapmeRs抑制hsa-piR-32877对人急性髓细胞白血病细胞增殖和凋亡的影响。

International Journal of Molecular and Cellular Medicine Pub Date : 2023-01-01 DOI: 10.22088/IJMCM.BUMS.12.1.18

Sepideh Nasseri, Mohammadreza Sharifi, Valiollah Mehrzad

{"title":"Effects of hsa-piR-32877 Suppression with Antisense LNA GapmeRs on the Proliferation and Apoptosis of Human Acute Myeloid Leukemia Cells.","authors":"Sepideh Nasseri, Mohammadreza Sharifi, Valiollah Mehrzad","doi":"10.22088/IJMCM.BUMS.12.1.18","DOIUrl":"10.22088/IJMCM.BUMS.12.1.18","url":null,"abstract":"Acute myeloid leukemia (AML) is an invasive form of hematologic malignancies which results in the overproduction of myeloid cells in the bone marrow. Aberrant expression of piwi-interacting RNAs (piRNAs) which belong to small non-coding RNAs, play important roles in different cancer cells' progress. hsa- piR- 32877 is up-regulated in AML. Down regulation of hsa-piR-32877 by antisense LNA GapmeRs could be potential for suppression of myeloid cell proliferation and induce myeloid cell apoptosis. We have blocked the expression of hsa-piR-32877 by antisense LNA GapmeRs in human bone marrow blast cells, and the M-07e cell line. Samples were transfected with antisense LNA GapmeRs at 24, 48, and 72 hours. The Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to investigate the expression of hsa-piR-32877, CASP3, and CASP9. Both CASP3 and CASP9 play important roles in apoptosis. Cell proliferation was studied via CFSE (carboxyfluorescein diacetate succinimidyl ester) assay. Results showed that hsa-piR-32877 was down-regulated by antisense LNA GapmeRs in the patient and cell line samples. Also, after transfection, cell proliferation and apoptosis decreased and increased, respectively. Our data suggested that hsa-piR-32877 suppression may act as a novel therapeutic method for the inhibition of human leukemic cells proliferation in AML.","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"12 1","pages":"18-29"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71521382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sex-based Dysregulation of Inflammation-related Genes in Periodontitis. 牙周炎中炎症相关基因的性别失调

International Journal of Molecular and Cellular Medicine Pub Date : 2023-01-01 DOI: 10.22088/IJMCM.BUMS.12.3.300

Soudeh Ghafouri-Fard, Leila Gholami, Elham Badrlou, Saba Sadeghpour, Naghme Nazer, Mahdi Shadnoush, Sheyda Khalilian, Arezou Sayad

{"title":"Sex-based Dysregulation of Inflammation-related Genes in Periodontitis.","authors":"Soudeh Ghafouri-Fard, Leila Gholami, Elham Badrlou, Saba Sadeghpour, Naghme Nazer, Mahdi Shadnoush, Sheyda Khalilian, Arezou Sayad","doi":"10.22088/IJMCM.BUMS.12.3.300","DOIUrl":"10.22088/IJMCM.BUMS.12.3.300","url":null,"abstract":"Periodontitis is a chronic inflammatory condition affecting a large population all over the world. This condition is linked with abnormal expression of numerous genes. We measured levels of CYFIP1, KDR, RABGGTA, RABGGTB and FOXD2 in gingival tissue and circulation of people with periodontitis and healthy controls. KDR was more expressed in tissue samples of female patients compared with female controls (Ratio of mean expression (RME) =4.16, P=0.02). However, this gene was less expressed in the blood of female patients compared with female control subjects (RME=0.12, P=0.04). RABGGTB was less expressed in the blood of male patients compared with male controls (RME=0.20, P=0.02). Finally, FOXD2 was less expressed in total blood samples compared with total controls (RME=0.3, P<0.001) and in blood samples of female patients compared with female control subjects (RME=0.02, P<0.001). RABGGTA had the best area under curve (AUC) value in differentiation of patients' tissues from normal tissues (AUC=0.60, sensitivity=0.37, specificity=0.92). In distinction of abnormal blood samples from controls, FOXD2 had the best performance (AUC=0.85, sensitivity=0.66, specificity=0.91). In brief, we demonstrated a sex-dependent dysregulation of KDR, RABGGTB and FOXD2 genes in circulation or tissue of patients with periodontitis.","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"12 3","pages":"300-309"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CD44 rs13347C>T Variants in 3'UTR and Prostate Neoplasms: A Case-control Study and Bioinformatics Approach. 3'UTR 中的 CD44 rs13347C>T 变异与前列腺肿瘤：病例对照研究和生物信息学方法。

International Journal of Molecular and Cellular Medicine Pub Date : 2023-01-01 DOI: 10.22088/IJMCM.BUMS.12.3.275

Emadoddin Moudi, Mohammadkazem Heydari, Abasalt Hosseinzadeh Colagar

{"title":"CD44 rs13347C>T Variants in 3'UTR and Prostate Neoplasms: A Case-control Study and Bioinformatics Approach.","authors":"Emadoddin Moudi, Mohammadkazem Heydari, Abasalt Hosseinzadeh Colagar","doi":"10.22088/IJMCM.BUMS.12.3.275","DOIUrl":"10.22088/IJMCM.BUMS.12.3.275","url":null,"abstract":"CD44, a cell-surface receptor and a key player in cellular signaling, can act as both tumor suppressor and promoter. This study aimed to investigate the association of CD44 rs13347C>T variants with prostate neoplasms, including both benign prostatic hyperplasia (BPH) and prostate cancers using a case-control and bioinformatics approach. Genomic DNA was extracted from 545 blood samples (225 BPH, 225 prostate cancers, and 95 control) and the CD44 rs13347C>T genotypes were identified using PCR-RFLP. We explored miRNA interactions using the miRNASNP-v3 database and GeneMANIA for co-expression networks. Results showed cancer patients had significantly higher PSA levels compared to both controls (p= 0.03) and BPH (p= 0.01). Additionally, digital rectal examination-positive and smoker BPH patients showed significantly the increased cancer risk (p= 0.004, p= 0.046). Prostate cancer group indicated significantly higher frequency of CD44 rs13347C>T mutant allele compared to control and BPH groups, particularly in TT and CT+TT genotypes (p < 0.05). miRNA SNP-v3 database predicted the mutant allele of CD44 rs13347C>T could lose 1 and gain 6 miRNAs for a new site created. Co-expression analysis revealed a direct interaction between CD44 and aryl hydrocarbon receptor (AHR), a gene known to be dysregulated in smokers. Furthermore, these genes alone display co-expression interactions with integrin subunit alpha 4 (ITGA4), protein plays a paradoxical role, both suppressing and promoting tumors. Based on the findings, the mutant allele of CD44 rs13347C>T may disrupt miRNA binding, which may potentially impact CD44, AHR, and ITGA4 expression in smokers, possibly contributing to prostate cancer progression.","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"12 3","pages":"275-287"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

EBV and HPV Infections in Colorectal Cancer and Their Effect on P53 and P16 Protein Expression. 结直肠癌中的 EBV 和 HPV 感染及其对 P53 和 P16 蛋白表达的影响

International Journal of Molecular and Cellular Medicine Pub Date : 2023-01-01 DOI: 10.22088/IJMCM.BUMS.12.3.288

Arefeh Ebrahimian Shiadeh, Vahideh Hamidi Sofiani, Saghar Saber Amoli, Mahdie Taheri, Alijan Tabarraei, Hadi Razavi Nikoo, Farzin Sadeghi, Sorayya Khafri, Ghodsieh Kamrani, Yousef Yahyapour, Abdolvahab Moradi

{"title":"EBV and HPV Infections in Colorectal Cancer and Their Effect on P53 and P16 Protein Expression.","authors":"Arefeh Ebrahimian Shiadeh, Vahideh Hamidi Sofiani, Saghar Saber Amoli, Mahdie Taheri, Alijan Tabarraei, Hadi Razavi Nikoo, Farzin Sadeghi, Sorayya Khafri, Ghodsieh Kamrani, Yousef Yahyapour, Abdolvahab Moradi","doi":"10.22088/IJMCM.BUMS.12.3.288","DOIUrl":"10.22088/IJMCM.BUMS.12.3.288","url":null,"abstract":"Viral infections contribute to 15-20% of newly diagnosed cancers worldwide. There is evidence of a possible etiological role of Epstein-Barr virus (EBV) and high-risk human papillomaviruses (HR-HPVs) in colorectal carcinoma (CRC). Loss of p53 and p16 function has been found in many cancers and this may occur in many different ways, including gene mutation or interaction with viral oncoproteins. This study aimed to evaluate the presence of EBV and HPV in CRC patients in northern Iran and to assess p53 and p16 protein expression related to these viral infections. Real-time PCR was used to amplify the DNA sequences of these viruses in 55 colorectal tumoral tissues, along with their corresponding non-tumoral adjacent tissues. Additionally, immunohistochemistry (IHC) was utilized to determine p53 and p16 protein expression. EBV DNA was detected in 49.1% of CRC tissues. Furthermore, HPV DNA was present in 7.3% of CRC tissues. Notably, the prevalence of EBV infection in tumoral tissues was significantly higher than in non-tumoral tissues (P=0.001). The EBV DNA polymerase catalytic subunit (BALF5) copy number in tumoral tissues was higher than in non-tumoral tissues and this difference was statistically significant (P=0.008). P53 was positive in 21/26 (80.8%) EBV-positive and in 11/25 (44%) EBV-negative samples and this difference was significant (P=0.007). P16 was positive in 13/26 (50%) EBV-positive and in 14/25 (58.3%) EBV-negative samples (P= 0.668). Our findings suggest that EBV infection can increase the risk of CRC. In addition, EBV seems to stabilize p53 in EBV-positive CRC which needs further research. No significant correlation was detected between EBV infection and p16 expression. Also, we could not find a causal relationship between HPV infection and CRC in the study population.","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"12 3","pages":"288-299"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Combination Therapy in Cancer: Doxorubicin in Combination with an N-terminal Peptide of Endostatin Suppresses Angiogenesis and Stimulates Apoptosis in the Breast Cancer. 癌症联合疗法：多柔比星与内抑素 N-末端肽联用可抑制血管生成并刺激乳腺癌细胞凋亡

International Journal of Molecular and Cellular Medicine Pub Date : 2023-01-01 DOI: 10.22088/IJMCM.BUMS.12.2.120

Narges Sarabi, Reyhane Chamani, Elham Assareh, Omid Saberi, S Mohsen Asghari

{"title":"Combination Therapy in Cancer: Doxorubicin in Combination with an N-terminal Peptide of Endostatin Suppresses Angiogenesis and Stimulates Apoptosis in the Breast Cancer.","authors":"Narges Sarabi, Reyhane Chamani, Elham Assareh, Omid Saberi, S Mohsen Asghari","doi":"10.22088/IJMCM.BUMS.12.2.120","DOIUrl":"10.22088/IJMCM.BUMS.12.2.120","url":null,"abstract":"The combination of chemotherapy drugs with angiogenesis inhibitors improves response and survival and reduces the cytotoxic side effects and drug resistance in patients compared to chemotherapy alone. Here, we investigated the efficacy of the concomitant administration of doxorubicin and a peptide derived from the N-terminal domain of Endostatin (called ES-SS) in the 4T1 mammary carcinoma tumor model. Tumor-bearing mice were divided into the control and three treatment groups, including ES-SS, doxorubicin, and the combination. Injections were performed daily for two weeks and tumor volumes were measured during the treatment. Immunohistochemical analysis of Ki-67, CD31, CD34, Bcl-2, p53 expression, and TUNEL assay were performed on tumor tissues at the end of treatment. Besides, molecular dynamics and docking simulations were performed. It was demonstrated that tumor growth was inhibited in mice treated with peptide plus doxorubicin more significantly than in each treatment alone (P<0.05). No weight loss or adverse effects were observed. Moreover, combination therapy was more effective in tumor angiogenesis suppression and apoptosis stimulation (P<0.05). Docking simulations by ClusPro server demonstrated that ES-SS binds to integrin α5β1, Transglu-taminase 2, and Matrix metalloproteinase 2 with more negative binding energy and hydrogen bonds compared to the native peptide. Generally, we proposed that ES-SS can augment the therapeutic efficacy of doxorubicin through angiogenesis prevention and apoptosis induction in breast tumor. Owing to the advantages of peptides to recombinant proteins or monoclonal antibodies, further preclinical and clinical evaluations of this combination strategy are worth taking into consideration.","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"12 2","pages":"120-134"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10837914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139681095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Isoproterenol Alters Metabolism, Promotes Survival and Migration in 5-Fluorouracil-Treated SW480 Cells with and without Beta-hydroxybutyrate. 异丙肾上腺素能改变经 5-氟尿嘧啶处理的 SW480 细胞的新陈代谢，促进其存活和迁移，无论其是否含有 β-羟丁酸。

International Journal of Molecular and Cellular Medicine Pub Date : 2023-01-01 DOI: 10.22088/IJMCM.BUMS.12.2.144

Azam Shakery, Katayoun Pourvali, Ghazaleh Shimi, Hamid Zand

{"title":"Isoproterenol Alters Metabolism, Promotes Survival and Migration in 5-Fluorouracil-Treated SW480 Cells with and without Beta-hydroxybutyrate.","authors":"Azam Shakery, Katayoun Pourvali, Ghazaleh Shimi, Hamid Zand","doi":"10.22088/IJMCM.BUMS.12.2.144","DOIUrl":"10.22088/IJMCM.BUMS.12.2.144","url":null,"abstract":"People with cancer often experience long-term physical and psychological stress, which can have a significant impact on tumor metabolism and treatment. The effects of adrenergic signaling on metabolic pathways are well known, but only a few studies have looked into the connection between this signaling and tumor metabolism. This study examined the effects of treatment with isoproterenol (Iso) alone and in combination with β-hydroxybutyrate (βHB), a mitochondrial fuel, on the metabolism, survival, and migration of SW480 colon cancer cells treated with 5-fluorouracil (5FU). The researchers measured the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) to determine the metabolic profile of these cells. They also analyzed the gene expression of PGC-1α, c-MYC, and NANOG to investigate the relationship between metabolic phenotype and stemness status. Scratch assays were used to assess cell migration. The results showed that Iso treatment increased cell viability in both SW480 and 5FU-treated SW480 cells. There was a significant decrease in ECAR and an increase in OCR after Iso treatment in both cell types. The expression of c-MYC and NANOG, genes associated with stemness, increased, while the expression of PGC-1α, a gene related to oxidative phosphorylation, decreased following Iso treatment. Iso treatment also increased the migration potential of both SW480 and 5FU-treated SW480 cells. These findings suggest that under stressful conditions, 5FU-treated colon cancer cells can utilize the oxidative phosphorylation pathway for growth and migration.","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"12 2","pages":"144-158"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10837909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139681100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of Drug Resistance in the Tamoxifen-treated MKN-45 Gastric Cancer Cell Line via the Epithelial-mesenchymal Transition Signaling Pathway. 通过上皮-间质转化信号通路评估他莫昔芬治疗的 MKN-45 胃癌细胞系的耐药性

IF 1.5

International Journal of Molecular and Cellular Medicine Pub Date : 2023-01-01 DOI: 10.22088/IJMCM.BUMS.12.4.361

Zeinab Mahdian, Mahdi Pouramir, Hassan Akrami, Ebrahim Zabihi

{"title":"Evaluation of Drug Resistance in the Tamoxifen-treated MKN-45 Gastric Cancer Cell Line via the Epithelial-mesenchymal Transition Signaling Pathway.","authors":"Zeinab Mahdian, Mahdi Pouramir, Hassan Akrami, Ebrahim Zabihi","doi":"10.22088/IJMCM.BUMS.12.4.361","DOIUrl":"10.22088/IJMCM.BUMS.12.4.361","url":null,"abstract":"One of the major challenges in gastric cancer (GC) chemotherapy is the phenomenon of multi-drug resistance (MDR). The epithelial-mesenchymal transition (EMT) and its key molecules, transforming growth factor-β (TGFβ) and SMAD2, play a central role in MDR occurrence. Tamoxifen (TAM), a triphenylethylene derivative, can overcome MDR in human gastric cancers. The aim of this study was to investigate the effect of TAM on 5-FU resistance of GC by suppressing the TGFβ1/SMAD2 signaling pathway and EMT. The MKN-45 cell line was subjected to treatment with 5-FU, TAM and a combination of both. The MTT assay was used to investigate the cytotoxic effects of 5-FU and TAM, and the DNA laddering technique was used to assess DNA fragmentation and apoptosis. Real-time RT-PCR examined the change in gene expression in EMT-related genes (SNAI2, VIM, TGFβ1 and SMAD2). The results of the present study indicated that not only TAM treatment significantly decreased the IC50 of 5-FU (P≤0.05), but also the addition of TAM to 5-FU induced apoptosis in the MKN-45 cell line. Treatment with TAM and 5-FU significantly inhibited TGFβ1 and TGFβ1-induced expression of EMT markers (VIM and SNAI2) in MKN-45 cells (P≤0.05). The reduction of TGFβ1 targets downstream of the SMAD2 signaling pathway reversed the process of EMT and significantly increased the sensitivity of MKN-45 cells to 5-FU. The results of the present study suggested that reversal of EMT-mediated MDR via the TGFβ1/SMAD signaling pathway using TAM may be a potential new therapeutic strategy to overcome chemoresistance to 5-FU during GC chemotherapy.","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"12 4","pages":"361-371"},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11240059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0