Fig 3 - available via license: Creative Commons Attribution 4.0 International
Content may be subject to copyright.
SGC7901/DOX cells underwent EMT mediated by upregulation of Akt signaling pathway. a Images were captured by Olympus IX71 inverted microscope system. Morphological observation showed morphological variance between SGC7901/DOX and SGC7901 cells. The Scale bar represents 10 μm. b SGC7901 and SGC7901/DOX cells were left DOX-untreated for 48 h for Western blot assay, measeuring EMT-related proteins and Akt expression. Bar diagram shows the relative expressions of proteins normalized to GAPDH. Data are represented as mean ± SD of three independent experiments (n = 3, *** p < 0.001; ** p < 0.01; * p < 0.05: NS means not significant, p > 0.05). c Immunofluorescence assay was used to detect EMT-associated proteins in SGC7901/DOX cells. E-cadherin, β-catenin, and vimentin were stained red and nuclei stained with DAPI were blue. The white arrow indicates β-catenin nuclear tranlocation. Images were captured at 1800× magnification
Source publication
Background:
Gastric cancer is one of the major causes of cancer-related mortality worldwide. Most of patients presenting with inoperable gastric cancers rely on systemic chemotherapy for prolongation of survival. Doxorubicin (DOX) is one of the important agents against gastric cancer. Acquired DOX-resistance severely impedes the chemotherapeutic e...
Contexts in source publication
Context 1
... has been illustrated as a critical regulator in cell mi- gration and drug resistance. Morphological observation showed that the parental SGC7901 cells were generally round or oval, but most of SGC7901/DOX cells trans- formed into spindle shape (Fig. 3a). The expression of EMT associated markers was measured by western blot. SGC7901/DOX cells were found to undergo EMT process for it expressed higher mesenchymal cell markers including β-catenin and vimentin while losing epithelial cell adhesion molecule such as E-cadherin. In addition, Akt was activated in SGC7901/DOX cells (Fig. 3b). ...
Context 2
... spindle shape (Fig. 3a). The expression of EMT associated markers was measured by western blot. SGC7901/DOX cells were found to undergo EMT process for it expressed higher mesenchymal cell markers including β-catenin and vimentin while losing epithelial cell adhesion molecule such as E-cadherin. In addition, Akt was activated in SGC7901/DOX cells (Fig. 3b). EMT markers were also verified through im- munofluorescent assay. Long-term DOX incubation de- creased E-cadherin cytomembrane expression whereas increased vimentin expression in cytoplasm and enhanced β-catenin nuclear tranlocation (Fig. ...
Context 3
... cell adhesion molecule such as E-cadherin. In addition, Akt was activated in SGC7901/DOX cells (Fig. 3b). EMT markers were also verified through im- munofluorescent assay. Long-term DOX incubation de- creased E-cadherin cytomembrane expression whereas increased vimentin expression in cytoplasm and enhanced β-catenin nuclear tranlocation (Fig. ...
Context 4
... by the acquisition of drug re- sistance and enhancive migration (Fig. 2). And mean- while, SGC7901/DOX cells displayed an apparent EMT potential for they were transformed into spindle-like shape, and expressed high level of mesenchymal cell markers including β-catenin and vimentin while losing epithelial cell adhesion molecule such as E-cadherin (Fig. ...
Similar publications
Citations
... Combining GST-π with lipophilic cytotoxic medicines might enhance water solubility and facilitate drug efflux, thereby reducing the lethal impact of anti-cancer medications [62]. resistant cell line SCG7901 exhibited EMT and overexpressed the cellular-mesenchymal to epithelial transition factor (c-MET) [63,64]. E-cadherin, a suppressor of EMT, is not present in drug-resistant cells. ...
One of the most prevalent types of cancer worldwide today is gastric intestinal (GI) tumors. To guarantee their lives, people with a developed GI require palliative care. This covers the application of targeted medicines in addition to chemotherapy treatments including cisplatin, 5-fluorouracil, oxaliplatin, paclitaxel, and pemetrexed. Because of the evidence of drug resistance emerging in poor patient outcomes and prognoses, determining the exact process of medication resistance is motivated. Besides, it is noteworthy that exosomes and noncoding RNAs, like microRNAs and long non-coding RNAs (lncRNAs), produced from tumor cells are implicated in both GI medication resistance and the carcinogenesis and development of GI disease. Biochemical events related to the cell cycle, differentiation of cells, growth, and pluripotency, in addition to gene transcription, splicing, and epigenetics, are all regulated by noncoding RNAs (ncRNAs). Therefore, it should come as a wonder that several ncRNAs have been connected in recent years to drug susceptibility and resistance as well as tumorigenesis. Additionally, through communicating directly with medications, altering the transcriptome of tumor cells, and affecting the immune system, exosomes may govern treatment resistance. Because of this, exosomal lncRNAs often act as a competitive endogenous RNA (ceRNA) of miRNAs to carry out its role in modifying drug resistance. In light of this, we provide an overview of the roles and processes of ncRNA-enriched exosomes in GI medication resistance.
... Resveratrol induced apoptosis in gastric cancer cells via NF-κB down-regulation leading to a decrease in the level of anti-apoptotic factor Bcl-2 and an increase in apoptotic factors caspase-3 and caspase-8 [76]. Resveratrol inhibited doxorubicin resistance in gastric cancer cells by stimulation of PTEN/Akt signaling pathway [77]. In addition, the results of Howells et al. demonstrated a significantly increased in the expression of cleaved caspase-3, apoptotic marker, in colorectal cancer patient's tissue after treatment with pure resveratrol compared with placebo [41]. ...
Background
Gastrointestinal cancer (GIC) ranks as the highest cause of cancer-related deaths globally. GIC patients are often diagnosed at advanced stages, limiting effective treatment options. Chemotherapy, the common GIC recommendation, has significant disadvantages such as toxicity and adverse effects. Natural products contain substances with diverse pharmacological characteristics that promise for use in cancer therapeutics. In this study, the flower of renowned Asian medicinal plant, Shorea roxburghii was collected and extracted to investigate its phytochemical contents, antioxidant, and anticancer properties on GIC cells.
Methods
The phytochemical contents of Shorea roxburghii extract were assessed using suitable methods. Phenolic content was determined through the Folin-Ciocalteu method, while flavonoids were quantified using the aluminum chloride (AlCl3) method. Antioxidant activity was evaluated using the FRAP and DPPH assays. Cytotoxicity was assessed in GIC cell lines via the MTT assay. Additionally, intracellular ROS levels and apoptosis were examined through flow cytometry techniques. The correlation between GIC cell viability and phytochemicals, ¹H-NMR analysis was conducted.
Results
Among the four different solvent extracts, ethyl acetate extract had the highest phenolic and flavonoid contents. Water extract exhibited the strongest reducing power and DPPH scavenging activity following by ethyl acetate. Interestingly, ethyl acetate extract demonstrated the highest inhibitory activity against three GIC cell lines (KKU-213B, HepG2, AGS) with IC50 values of 91.60 µg/ml, 39.38 µg/ml, and 35.59 µg/ml, while showing less toxicity to normal fibroblast cells. Ethyl acetate extract induced reactive oxygen species and apoptosis in GIC cell lines by downregulating anti-apoptotic protein Bcl-2. Metabolic profiling-based screening revealed a positive association between reduced GIC cell viability and phytochemicals like cinnamic acid and its derivatives, ferulic acid and coumaric acid.
Conclusions
This study highlights the potential of natural compounds in Shorea roxburghii in the development of more effective and safer anticancer agents as options for GIC as well as shedding light on new avenues for cancer treatment.
... 69 Additionally, it promotes cell invasion by regulating the E-cadherin/β-catenin complex, exerting a more critical impact on the metastatic process than the complex itself. 70 PL was shown to significantly inhibit HCC by impeding EMT. In previous studies, PL inhibited HCC tumor angiogenesis, invasion, and metastasis, and induced autophagy-apoptosis interaction. ...
Background/Aims
Plumbagin (PL) has been shown to effe ctively inhibit autophagy, suppressing invasion and migration of hepatocellular carcinoma (HCC) cells. However, the specific mechanism remains unclear. This study aimed to investigate the effect of PL on tumor growth factor (TGF)-β-induced epithelial-mesenchymal transition (EMT) in HCC.
Methods
Huh-7 cells were cultured, and in vivo models of EMT and HCC-associated lung metastasis were developed through tail vein and in situ injections of tumor cells. In vivo imaging and hematoxylin and eosin staining were used to evaluate HCC modeling and lung metastasis. After PL intervention, the expression levels of Snail, vimentin, E-cadherin, and N-cadherin in the liver were evaluated through immunohistochemistry and Western blot. An in vitro TGF-β-induced cell EMT model was used to detect Snail, vimentin, E-cadherin, and N-cadherin mRNA levels through a polymerase chain reaction. Their protein levels were detected by immunofluorescence staining and Western blot.
Results
In vivo experiments demonstrated that PL significantly reduced the expression of Snail, vimentin, and N-cadherin, while increasing the expression of E-cadherin at the protein levels, effectively inhibiting HCC and lung metastasis. In vitro experiments confirmed that PL up-regulated epithelial cell markers, down-regulated mesenchymal cell markers, and inhibited EMT levels in HCC cells.
Conclusion
PL inhibits Snail expression, up-regulates E-cadherin expression, and down-regulates N-cadherin and vimentin expression, preventing EMT in HCC cells and reducing lung metastasis.
... RES prevents epithelial-mesenchymal transition (EMT) and improves the DOX-resistance of gastric cancer through the modulation of PTEN/Akt signaling pathway [23]. RES can repress hypoxia-induced resistance to doxorubicin found in breast cancer cells by decreasing HIF-1α protein expression [24]. ...
Objectives:
This research aims to comparatively investigate the capability of resveratrol (RES) and RES analogues, oxyresveratrol (Oxy-RES) and dihydrooxyresveratrol (DHoxy-RES), to potentiate doxorubicin (DOX) effects against lung carcinoma epithelial cells.
Methods:
All experiments were performed on lung carcinoma cell lines (A549) with DOX combination between DOX and RES or RES analogues. Cell viability or growth inhibitory effect was assessed by MTT assay and genes associated with survival and metastasis were monitored by real-time polymerase chain reaction (RT-PCR).
Results:
DOX obviously demonstrated cytotoxic and anti-metastatic activities against A549 cells. Expression of gene-associated with both activities was potentiated by RES and RES analogues. Oxy-RES showed highest capability to potentiate DOX effects. DHoxy-RES showed nearly no effect to DOX activities.
Conclusions:
These results provided an important basis of DOX combination with RES analogues, especially Oxy-RES, for better therapeutic effect. Further studies in human should be performed on exploring combination of DOX and Oxy-RES.
... We next found that TPN10475 inhibited the proliferation of murine CD4 + T cells in a dose-dependent manner (Fig. 1E). In addition, in order to rule out the effect of the activation and proliferation of CD4 + T cells due to the toxicity of TPN10475, the CCK8 assay, which is commonly used to identify cell viability and as an indicator to assess cytotoxicity (Xu et al. 2017), was found to have no cytotoxic effect on 293T cells using three concentrations of TPN10475 (Fig. 1J). Detection of necrotic CD4 + T cells by PI staining revealed that TPN10475 had no effect on apoptosis, and even the survival percentage of CD4 + T cells activated by TCR signaling was higher than that of unstimulated cells ( Fig. 1K and L). ...
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) mediated by immune cells, in which auto-reactive CD4⁺ T cells have been implicated as a major driver in the pathogenesis of the disease. In this study, we aimed to investigate whether the artemisinin derivative TPN10475 could alleviate experimental autoimmune encephalomyelitis (EAE), a commonly used animal model of MS and its possible mechanisms. TPN10475 effectively resisted the reduction of TGF-β signal transduction induced by TCR stimulation, suppressed the activation and function of effector CD4⁺ T cells in vitro, and restricted the differentiation of pathogenic Th1 and Th17 cells. It was also found to negatively regulate the inflammatory response in EAE by reducing the peripheral activation drive of auto-reactive helper T lymphocytes, inhibiting the migration of inflammatory cells into the CNS to attenuate EAE. The above results suggested that the upregulation of TGF-β signal transduction may provide new ideas for the study of MS pathogenesis and have positive implications for the development of drugs for the treatment of autoimmune diseases.
Graphical Abstract
TPN10475 promotes TGF-β signaling under TCR stimulation, restricts the proliferation and activation of effector CD4⁺ T cells, inhibits the differentiation of pathogenic Th1 and Th17 cells, negatively regulates the inflammatory response and suppresses the migration of inflammatory cells to the CNS, thereby alleviating EAE. The figure was created with Biorender.com (Agreement number: ME25MXMB52).
... Many plants, including grapes, mulberries and peanuts, produce RES in reaction to harmful circumstances like stress, UV irradiation, and fungal diseases [64][65][66]. Several studies have indicated that, mechanisms underlying the hepatoprotective potential of RES may be combinations of anti-oxidant, antiinflammatory, antimutagenic, reversal of EMT, influence on the cell cycle and cell differentiation, induction of apoptosis and suppression of proliferation playing roles in the initiation and secondary modification stages of neoplastic development [67][68][69][70][71][72]. RES was able to suppress chemical-induced carcinogenesis, relying on its inhibitory action of CYP450 dependent oxidase detoxification and elimination by up-regulating catalase and superoxide dismutase activities [73,74]. ...
... According to previous literature, there have been copious preclinical and clinical reports supporting the central role of reactive oxygen and nitrogen species (RONS) in CAP treatment of various types of cancer, such as breast, melanoma, ovarian, metastatic bone, pancreatic, oral, and thyroid cancers [7][8][9][10][11][12][13]. Because the free radicals induced by cold atmospheric plasma have hemolytic activity on red blood cells, the mild conditions of ROS/RNS induced by CAP are necessary for the safe treatment of human diseases. CAP demonstrates great potential in cancer therapy by selectively inducing apoptosis in tumor cells and inhibiting their migration and invasion [14]. However, the precise underlying CAP's therapeutic advantages in oncology is not completely elucidated. ...
Head and neck cancer (HNC) is the seventh most prevalent cancer globally, often characterized by chemo-resistance and immunosuppression, which significantly hampers treatment efficacy. Cold atmospheric plasma (CAP) has recently emerged as a promising adjuvant oncotherapy with substantial potential and advantages. In this study, Piezobrush® PZ2, a handheld CAP unit based on the piezoelectric direct discharge technology, was used to generate and deliver non-thermal plasma. We aimed to investigate the effects of CAPPZ2 on various types of HNC cells and elucidate the underlying mechanisms. In addition, we endeavored to examine the efficacy of combining CAPPZ2 with chemotherapy drugs (i.e., cisplatin) or immune checkpoint blockade (ICB, i.e., PD1 antibody) in HNC treatment. Firstly, the results demonstrated that CAPPZ2 exerted anti-neoplastic functions through inhibiting cell proliferation, migration and invasion, and promoting apoptosis and autophagy. Secondly, using transcriptomic sequencing, Western blotting, and quantitative real-time PCR, the mechanisms underlying CAPPZ2 treatment in vitro was presumed to be a multitargeted blockade of major cancer survival pathways, such as redox balance, glycolysis, and PI3K/AKT/mTOR/HIF-1α signaling. Lastly, combinatorial thearpy containing CAPPZ2 and cisplatin or PD-1 antibody significantly suppressed tumor growth and prolonged recipient survival in vivo. Collectively, the synergistic effects of CAPPZ2 and cisplatin or PD-1 antibody could serve as a promising solution to enhance head and neck tumor elimination.
... Alexander A. Minin Department of Cell Biology, Institute of Protein Research, Russian Academy of Sciences, Moscow, Russia *Address all correspondence to: minin@vega.protres.ruand gastric cancer cells SGC7901[31]. Noteworthy, the reversal of EMT in these cells with concomitant decrease of vimentin expression caused a reduction of doxorubicin resistance[6,30,31]. ...
... gastric cancer cells SGC7901[31]. Noteworthy, the reversal of EMT in these cells with concomitant decrease of vimentin expression caused a reduction of doxorubicin resistance[6,30,31]. ...
Vimentin is a cytoskeleton protein of type III intermediate filaments (IFs) that is expressed in mesenchymal cells. Unlike other tissue-specific IF proteins vimentin may be found in different cell types. Thus, the expression of vimentin is a hallmark of an epithelial-to-mesenchymal transition (EMT), which is observed during early embryogenesis, wound healing, and the malignant transformation of various tumor cells. Besides the well-established function of vimentin IFs to provide the mechanical strength of the cells, we discovered that their interaction with mitochondria causes the decrease of their motility and the elevation of the mitochondrial membrane potential. These observations suggested an idea that vimentin could play a role in stabilization of mitochondria in the harsh conditions of chemotherapy and thus protect cancer cells against oxidative stress. Doxorubicin is used for treating a wide range of human tumors, including gastric carcinoma, breast carcinoma, leukemia, lung cancer, malignant lymphoma and others. Though it has been used clinically for over five decades, precise molecular pathways leading to the cancer cell death remain unexplored. However, various mechanisms have been proposed including topoisomerase inhibition, oxidative stress, and redox cycling of doxorubicin in mitochondria. Here, we analyze the recent data demonstrating vimentin’s role in cell protection against doxorubicin.
... 36 In gastric cancer, resveratrol can inhibit EMT by regulating the PI3K/AKT signaling pathway, thereby reversing doxorubicin resistance. 37 The sensitivity of breast cancer to doxorubicin is also regulated by estrogen receptors to E-cadherin. 38 In this study, we revealed the link between DLX2 and doxorubicin resistance for the first time, and our results show that targeting DLX2 can significantly enhance the drug sensitivity of doxorubicin-resistant U-2OS cells and reduce CDH2 expression in drug-resistant cell lines. ...
Metastasis and doxorubicin resistance are challenges in the clinical diagnosis and treatment of osteosarcoma, the mechanisms underlying these phenomena remain unclear. In this study, we found that DLX2 is highly expressed in metastatic osteosarcoma and is closely related to clinical prognosis. Knockdown of DLX2 inhibited tumor proliferation and migration in vitro and inhibited tumor growth in vivo. Mechanistically, we found that DLX2 enhanced the repression of CDH2 transcription by binding to HOXC8, thereby promoting the epithelial-mesenchymal transition in osteosarcoma cells. Through subsequent exploration, we found that targeting DLX2/HOXC8 signaling significantly restores the sensitivity of osteosarcoma cells to doxorubicin. In conclusion, our findings demonstrate that DLX2 may enhance the transcriptional regulation of CDH2 through interacting with HOXC8, which in turn promotes epithelial-mesenchymal transition and doxorubicin resistance in osteosarcoma. These findings hold great potential for clinical application and may guide the development of novel targeted therapies for osteosarcoma.
... The presence of these cells is one of the main reasons for the failure of chemotherapy and the recurrence of cancers. Various studies suggested that suppressing EMT and stemness can be a helpful strategy for attenuating chemo-resistance and improving the efficiency of chemotherapy drugs [163,164]. It seems that zinc oxide nanoparticles can also have an inhibitory effect on EMT and stemness. ...
Cancer chemotherapy is still a serious challenge. Chemo-resistance and destructive side effects of chemotherapy drugs are the most critical limitations of chemotherapy. Chemo-resistance is the leading cause of chemotherapy failure. Chemo-resistance, which refers to the resistance of cancer cells to the anticancer effects of chemotherapy drugs, is caused by various reasons. Among the most important of these reasons is the increase in the efflux of chemotherapy drugs due to the rise in the expression and activity of ABC transporters, the weakening of apoptosis, and the strengthening of stemness. In the last decade, a significant number of studies focused on the application of nanotechnology in cancer treatment. Considering the anti-cancer properties of zinc, zinc oxide nanoparticles have received much attention in recent years. Some studies have indicated that zinc oxide nanoparticles can target the critical mechanisms of cancer chemo-resistance and enhance the effectiveness of chemotherapy drugs. These studies have shown that zinc oxide nanoparticles can reduce the activity of ABC transporters, increase DNA damage and apoptosis, and attenuate stemness in cancer cells, leading to enhanced chemo-sensitivity. Some other studies have also shown that zinc oxide nanoparticles in low doses can be helpful in minimizing the harmful side effects of chemotherapy drugs. In this article, after a brief overview of the mechanisms of chemo-resistance and anticancer effects of zinc, we will review all these studies in detail.
