scholarly journals CD147 supports paclitaxel resistance via interacting with RanBP1

Oncogene ◽  
2022 ◽  
Author(s):  
Gang Nan ◽  
Shu-Hua Zhao ◽  
Ting Wang ◽  
Dong Chao ◽  
Ruo-Fei Tian ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Protein Interactions ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Tunel Staining ◽  
Great Success ◽  
Variable Response ◽  
Paclitaxel Resistance ◽  
Paclitaxel Treatment

AbstractThough the great success of paclitaxel, the variable response of patients to the drug limits its clinical utility and the precise mechanisms underlying the variable response to paclitaxel remain largely unknown. This study aims to verify the role and the underlying mechanisms of CD147 in paclitaxel resistance. Immunostaining was used to analyze human non-small-cell lung cancer (NSCLC) and ovarian cancer tissues. RNA-sequencing was used to identify downstream effectors. Annexin V-FITC/propidium iodide and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to detect apoptosis. Co-immunoprecipitation (Co-IP), fluorescence resonance energy transfer (FRET) and surface plasmon resonance (SPR) were performed to determine protein interactions. Fluorescence recovery after photobleaching (FRAP) was performed to measure the speed of microtubule turnover. Xenograft tumor model was established to evaluate sensitivity of cancer cells to paclitaxel in vivo. In vitro and in vivo assays showed that silencing CD147 sensitized the cancer cells to paclitaxel treatment. CD147 protected cancer cells from paclitaxel-induced caspase-3 mediated apoptosis regardless of p53 status. Truncation analysis showed that the intracellular domain of CD147 (CD147ICD) was indispensable for CD147-regulated sensitivity to paclitaxel. Via screening the interacting proteins of CD147ICD, Ran binding protein 1 (RanBP1) was identified to interact with CD147ICD via its C-terminal tail. Furthermore, we showed that RanBP1 mediated CD147-regulated microtubule stability and dynamics as well as response to paclitaxel treatment. These results demonstrated that CD147 regulated paclitaxel response by interacting with the C-terminal tail of RanBP1 and targeting CD147 may be a promising strategy for preventing paclitaxel resistant.

scholarly journals Kinase shRNA screening reveals that TAOK3 enhances microtubule-targeted drug resistance of breast cancer cells via the NF-κB signaling pathway

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Tsung-Ching Lai ◽  
Chih-Yeu Fang ◽  
Yi-Hua Jan ◽  
Hsiao-Ling Hsieh ◽  
Yi-Fang Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Breast Cancer Cells ◽  
Breast Cancer Patients ◽  
Paclitaxel Resistance ◽  
Paclitaxel Treatment

Abstract Background Chemotherapy is currently one of the most effective treatments for advanced breast cancer. Anti-microtubule agents, including taxanes, eribulin and vinca-alkaloids are one of the primary major anti-breast cancer chemotherapies; however, chemoresistance remains a problem that is difficult to solve. We aimed to discover novel candidate protein targets to combat chemoresistance in breast cancer. Methods A lentiviral shRNA-based high-throughput screening platform was designed and developed to screen the global kinome to find new therapeutic targets in paclitaxel-resistant breast cancer cells. The phenotypes were confirmed with alternative expression in vitro and in vivo. Molecular mechanisms were investigated using global phosphoprotein arrays and expression microarrays. Global microarray analysis was performed to determine TAOK3 and genes that induced paclitaxel resistance. Results A serine/threonine kinase gene, TAOK3, was identified from 724 screened kinase genes. TAOK3 shRNA exhibited the most significant reduction in IC50 values in response to paclitaxel treatment. Ectopic downregulation of TAOK3 resulted in paclitaxel-resistant breast cancer cells sensitize to paclitaxel treatment in vitro and in vivo. The expression of TAOK3 also was correlated to sensitivity to two other anti-microtubule drugs, eribulin and vinorelbine. Our TAOK3-modulated microarray analysis indicated that NF-κB signaling played a major upstream regulation role. TAOK3 inhibitor, CP43, and shRNA of NF-κB both reduced the paclitaxel resistance in TAOK3 overexpressed cells. In clinical microarray databases, high TAOK3 expressed breast cancer patients had poorer prognoses after adjuvant chemotherapy. Conclusions Here we identified TAOK3 overexpression increased anti-microtubule drug resistance through upregulation of NF-κB signaling, which reduced cell death in breast cancer. Therefore, inhibition of the interaction between TAOK3 and NF-κB signaling may have therapeutic implications for breast cancer patients treated with anti-microtubule drugs.

scholarly journals Periplocin Extracted from Cortex Periplocae Induced Apoptosis of Gastric Cancer Cells via the ERK1/2-EGR1 Pathway

2016 ◽  
Vol 38 (5) ◽  
pp. 1939-1951 ◽  
Author(s):  
Lei Li ◽  
Lian-Mei Zhao ◽  
Su-li Dai ◽  
Wen-Xuan Cui ◽  
Hui-Lai Lv ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Inhibitory Effect ◽  
Tunel Staining ◽  
Dependent Manner ◽  
Gastric Cancer Cells ◽  
Induced Apoptosis

Background/Aims: Periplocin is extracted from the traditional herbal medicine cortex periplocae, which has been reported to suppress the growth of cancer cells. However, little is known about its effect on gastric cancer cells. Methods: Gastric cancer cells were treated with periplocin, and cell viability was assessed using MTS assay. Flow cytometry and TUNEL staining were performed to evaluate apoptosis, and protein expression was examined by western blotting. Microarray analysis was used to screen for changes in related genes. Results: We found that periplocin had an inhibitory effect on gastric cancer cell viability in a dose-dependent manner. Periplocin inhibited cell viability via the ERK1/2-EGR1 pathway to induce apoptosis. Periplocin also inhibited the growth of tumor xenografts and induced apoptosis in vivo. Conclusion: Our results show that periplocin inhibits the proliferation of gastric cancer cells and induces apoptosis in vitro and in vivo, indicating its potential to be used as an antitumor drug.

scholarly journals Transgenic Overexpression of IL-37 Protects Against Atherosclerosis and Strengthens Plaque Stability

2018 ◽  
Vol 45 (3) ◽  
pp. 1034-1050 ◽  
Author(s):  
Jing Liu ◽  
Jibin Lin ◽  
Shaolin He ◽  
Chun Wu ◽  
Boyuan Wang ◽  
...  
Keyword(s):  
Immunohistochemical Staining ◽  
Intracellular Cytokine Staining ◽  
Flow Cytometric Analysis ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Tunel Staining ◽  
Atherosclerotic Plaques ◽  
Plaque Stability ◽  
Atherosclerotic Burden

Background/Aims: Recently, studies have shown that interleukin-37 (IL-37) is involved in atherosclerosis-related diseases. However, the regulatory mechanisms of IL-37 in atherosclerosis remain unknown. This study aims to determine the role of IL-37 in atherosclerosis and to investigate the underlying mechanisms involved. Methods: IL-37 expression in human atherosclerotic plaques was detected by immunohistochemical staining and real-time reverse transcription polymerase chain reaction (RT-PCR). Oil Red O staining was used to measure the size of plaques. Cell apoptosis in vitro and in vivo was tested by flow cytometric analysis and terminal deoxynucleotidyl-transferase mediated dUTP nick-end labeling (TUNEL) staining, respectively. Protein expression levels of IL-37, IL-18Rα and p-Smad3 were measured by Weston blotting. Results: Immunohistochemical staining revealed that IL-37 was highly expressed in human atherosclerotic plaques. Intracellular cytokine staining revealed that infiltrated CD4+ T lymphocytes and vascular smooth muscle cells (VSMCs), but not macrophages, were the major sources of IL-37. Mice that overexpressed IL-37 exhibited significant improvements in their atherosclerotic burden, as demonstrated by reduced plaque size, increased collagen levels, and reduced numbers of apoptotic cells in vivo. Subsequently, mechanistic studies showed that IL-37 played an anti-atherosclerotic role, at least partially, through reducing inflammation by promoting the differentiation of the T helper cell anti-inflammatory phenotype, and through increasing plaque stability by decreasing matrix metalloproteinase (MMP)-2/13-mediated degradation of collagen and inhibiting VSMCs apoptosis. Conclusion: IL-37 may be a novel potential therapeutic target in patients with atherosclerotic heart disease.

Ginkgetin inhibits proliferation of human leukemia cells via the TNF-α signaling pathway

2017 ◽  
Vol 72 (11-12) ◽  
pp. 441-447 ◽  
Author(s):  
Ling-Ling Pan ◽  
Wen-Jun Wu ◽  
Gao-Feng Zheng ◽  
Xiao-Yan Han ◽  
Jing-Song He ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
K562 Cell ◽  
Lymphoblastic Leukemia ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Tunel Staining ◽  
Human Leukemia ◽  
Dependent Manner ◽  
Tnf Α

AbstractGinkgetin is known to be an anticancer agent in many studies. However, its effectiveness in treating chronic lymphoblastic leukemia (CLL) remains unknown. The present study aimed to evaluate the effects of ginkgetin on the growth of the K562 cell line. The MTT assay was employed to examine the proliferation of K562, and a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining was conducted to detect the apoptotic rates. Furthermore, changes of tumor necrosis factor-α (TNF-α) were detected by Western blot analysis. Ginkgetin inhibited the proliferation of K562 cells in a dose- and time-dependent manner. Concentrations of ginkgetin required to induce 50% death of K562 at 24, 48 and 72 h were 38.9, 31.3 and 19.2 μM, respectively. Moreover, treatment of ginkgetin increased K562 apoptosis in vitro along with increased levels of TNF-α. Interestingly, anti-TNF-α antibody prevented ginkgetin-induced K562 cell apoptosis and growth inhibition via deactivation of caspase-8, caspase-9 and caspase-3. Concomitantly, downregulation of TNF-α by etanercept in vivo attenuated ginkgetin-induced inhibitory effects on the tumor growth in an xenograft mouse model. Our results indicate that ginkgetin effectively inhibits K562 cell proliferation, and TNF-α plays a key role in ginkgetin-induced cell apoptosis.

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 Traditional Chinese Medication Qiliqiangxin Attenuates Diabetic Cardiomyopathy via Activating PPARγ

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaodong Wu ◽  
Ting Zhang ◽  
Ping Lyu ◽  
Mengli Chen ◽  
Gehui Ni ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Neonatal Rat ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Tunel Staining ◽  
Protective Mechanisms ◽  
Rat Cardiomyocytes ◽  
Induced Apoptosis ◽  
Hematoxylin Eosin

Background: Diabetic cardiomyopathy is the primary complication associated with diabetes mellitus and also is a major cause of death and disability. Limited pharmacological therapies are available for diabetic cardiomyopathy. Qiliqiangxin (QLQX), a Chinese medication, has been proven to be beneficial for heart failure patients. However, the role and the underlying protective mechanisms of QLQX in diabetic cardiomyopathy remain largely unexplored.Methods: Primary neonatal rat cardiomyocytes (NRCMs) were treated with glucose (HG, 40 mM) to establish the hyperglycemia-induced apoptosis model in vitro. Streptozotocin (STZ, 50 mg/kg/day for 5 consecutive days) was intraperitoneally injected into mice to establish the diabetic cardiomyopathy model in vivo. Various analyses including qRT-PCR, western blot, immunofluorescence [terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining] histology (hematoxylin–eosin and Masson's trichrome staining), and cardiac function (echocardiography) were performed in these mice. QLQX (0.5 μg/ml in vitro and 0.5 g/kg/day in vivo) was used in this study.Results: QLQX attenuated hyperglycemia-induced cardiomyocyte apoptosis via activating peroxisome proliferation-activated receptor γ (PPARγ). In vivo, QLQX treatment protected mice against STZ-induced cardiac dysfunction and pathological remodeling.Conclusions: QLQX attenuates diabetic cardiomyopathy via activating PPARγ.

scholarly journals Biomaterial-Modified Magnetic Nanoparticles γ-Fe2O3, Fe3O4 Used to Improve the Efficiency of Hyperthermia of Tumors in HepG2 Model

2021 ◽  
Vol 11 (5) ◽  
pp. 2017
Author(s):  
Shang Zhao ◽  
Seoksoon Lee
Keyword(s):  
Magnetic Nanoparticles ◽  
Cancer Cells ◽  
Experimental Studies ◽  
Protein Isolate ◽  
Superparamagnetic Nanoparticles ◽  
Great Success ◽  
Magnetic Nanoparticle Hyperthermia ◽  
Modified Magnetic Nanoparticles

The main treatments for cancer recorded to date include chemotherapy, radiotherapy, and surgery. Although we have achieved great success in treating certain types of tumors, there are still many incurable even with the help of modern treatments. Currently, the principles of magnetic-induction hyperthermia in magnetic nanoparticle hyperthermia are considered an effective treatment for cancer cells. As reported in previous articles, these nanoparticles generate a lot of heat that raises the temperatures of tumors, hence treating the cancer cells. The other significant potential of magnetic nanoparticles is the ability to combine heat and drug release for cancer treatment. However, within the biologically safe range of AC magnetic fields, the lack of induction heating power and the high criteria for biocompatibility in superparamagnetic-nanoparticle hyperthermia agents still make up the key challenges for the successful clinical application of magnetic hyperthermia. In this study, two different types of iron oxide nanoparticles (γ-Fe2O3, Fe3O4) were modified with whey protein isolate (WPI) to form bio-modified superparamagnetic nanoparticles with spherical or diamond-shaped structures and diameters between 20 and 100 nm, which demonstrate excellent stability under different conditions. Adriamycin (ADM) has also been successfully loaded onto these nanoparticles and used in this experiment. In vitro and in vivo experimental studies were performed using these WPI-modified nanoparticles on HepG2 tumor models and mice to assess their bioavailability and biological feasibility. The results prove that these WPI-modified nanoparticles perform satisfactorily in conjunction with hyperthermia to cure tumors completely.

scholarly journals Novel Protective Effects of Cistanche Tubulosa Extract Against Low-Luminance Blue Light-Induced Degenerative Retinopathy

2018 ◽  
Vol 51 (1) ◽  
pp. 63-79 ◽  
Author(s):  
Man-Ru Wu ◽  
Cheng-Hui Lin ◽  
Jau-Der Ho ◽  
George Hsiao ◽  
Yu-Wen  Cheng
Keyword(s):  
Western Blot ◽  
Blue Light ◽  
Immunofluorescent Staining ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Brown Norway ◽  
Tunel Staining ◽  
Rpe Cells ◽  
Cistanche Tubulosa

Background/Aims: Blue light-emitting diode light (BLL)-induced phototoxicity plays an important role in ocular diseases and causes retinal degeneration and apoptosis in human retinal pigment epithelial (RPE) cells. Cistanche tubulosa extract (CTE) is a traditional Chinese medicine with many beneficial protective properties; however, few studies have examined the ocular protective roles of CTE. In this study, we investigated the mechanisms underlying the effects of CTE on BLL-induced apoptosis in vitro and in vivo. Methods: RPE cells were applied in the current in vitro study and cell viability was determined by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis-related protein expression was determined by western blot analysis and immunofluorescence staining. Brown Norway rats were used to examine exposure to commercially available BLL in vivo. Hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and western blot assays were used to examine retinal morphological deformation. Results: CTE significantly inhibited hydrogen peroxide-, tert-butyl hydroperoxide-, sodium azide-, and BLL-induced RPE damage. Further, CTE reduced the expression of apoptotic markers such as cleaved caspase-3 and TUNEL staining after BLL exposure by inactivating apoptotic pathways, as shown via immunofluorescent staining. In addition, CTE inhibited the BLL-induced phosphorylation of c-Jun N-terminal kinase, extra signal-related kinases 1/2, and p38 in RPE cells. In vivo, the oral administration of CTE rescued 60-day periodic BLL exposure-induced decrements in retinal thickness and reduced the number of TUNEL-positive cells in the brown Norway rat model. Conclusion: CTE is a potential prophylactic agent against BLL-induced phototoxicity.

Sign in / Sign up

Export Citation Format

Share Document