Drug Information

Drug (ID: DG00597) and It's Reported Resistant Information
Name
Actinomycin D
Synonyms
Etoposide; Methotrexate; Actinomycin D; Cyclophosphamide; Vincristine
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Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Gestational trophoblastic neoplasia [ICD-11: 2C75]
[1]
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
Pituitary cancer [ICD-11: 2F37]
[2]
Target . NOUNIPROTAC [1]
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PubChem CID
457193
Type(s) of Resistant Mechanism of This Drug
  IDUE: Irregularity in Drug Uptake and Drug Efflux
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
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Gestational trophoblastic neoplasia [ICD-11: 2C75]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: SRY-box transcription factor 8 (SOX8) [1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Gestational trophoblastic neoplasia [ICD-11: 2C75.0]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell viability Activation hsa05200
Cell apoptosis Inhibition hsa04210
In Vitro Model JEG3 cells Brain Homo sapiens (Human) CVCL_0363
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 CCK-8 assay
Mechanism Description Over-expression of SOX8 promoted cell survival, enhanced soft agar clonogenesis, and attenuated caspase-3 activities after drug treatment in GTN cells. Importantly, SOX8 might be a potential regulator of reactive oxygen species (ROS) homeostasis, as SOX8 regulated the expression of antioxidant enzymes (GPX1, HMOX1) and reduced drug-induced ROS accumulation in GTN cell models. Collectively, SOX8 might promote drug resistance through attenuating the accumulation of ROS induced by chemotherapeutic drugs in GTN cells.
Key Molecule: SRY-box transcription factor 8 (SOX8) [1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Gestational trophoblastic neoplasia [ICD-11: 2C75.0]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell viability Activation hsa05200
Cell apoptosis Inhibition hsa04210
In Vitro Model JEG3 cells Brain Homo sapiens (Human) CVCL_0363
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 CCK-8 assay
Mechanism Description Over-expression of SOX8 promoted cell survival, enhanced soft agar clonogenesis, and attenuated caspase-3 activities after drug treatment in GTN cells. Importantly, SOX8 might be a potential regulator of reactive oxygen species (ROS) homeostasis, as SOX8 regulated the expression of antioxidant enzymes (GPX1, HMOX1) and reduced drug-induced ROS accumulation in GTN cell models. Collectively, SOX8 might promote drug resistance through attenuating the accumulation of ROS induced by chemotherapeutic drugs in GTN cells.
Key Molecule: SRY-box transcription factor 8 (SOX8) [1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Gestational trophoblastic neoplasia [ICD-11: 2C75.0]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell viability Activation hsa05200
Cell apoptosis Inhibition hsa04210
In Vitro Model JEG3 cells Brain Homo sapiens (Human) CVCL_0363
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 CCK-8 assay
Mechanism Description Over-expression of SOX8 promoted cell survival, enhanced soft agar clonogenesis, and attenuated caspase-3 activities after drug treatment in GTN cells. Importantly, SOX8 might be a potential regulator of reactive oxygen species (ROS) homeostasis, as SOX8 regulated the expression of antioxidant enzymes (GPX1, HMOX1) and reduced drug-induced ROS accumulation in GTN cell models. Collectively, SOX8 might promote drug resistance through attenuating the accumulation of ROS induced by chemotherapeutic drugs in GTN cells.
Key Molecule: SRY-box transcription factor 8 (SOX8) [1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Gestational trophoblastic neoplasia [ICD-11: 2C75.0]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell viability Activation hsa05200
Cell apoptosis Inhibition hsa04210
In Vitro Model JEG3 cells Brain Homo sapiens (Human) CVCL_0363
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 CCK-8 assay
Mechanism Description Over-expression of SOX8 promoted cell survival, enhanced soft agar clonogenesis, and attenuated caspase-3 activities after drug treatment in GTN cells. Importantly, SOX8 might be a potential regulator of reactive oxygen species (ROS) homeostasis, as SOX8 regulated the expression of antioxidant enzymes (GPX1, HMOX1) and reduced drug-induced ROS accumulation in GTN cell models. Collectively, SOX8 might promote drug resistance through attenuating the accumulation of ROS induced by chemotherapeutic drugs in GTN cells.
Pituitary cancer [ICD-11: 2F37]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [2]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Pituitary adenoma [ICD-11: 2F37.1]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model GH4C1 cells Pituitary gland Rattus norvegicus (Rat) CVCL_0276
Experiment for
Molecule Alteration		 Immunocytochemical staining assay
Experiment for
Drug Resistance		 Lowry assay; Bradford assay
Mechanism Description Cells resistant to colchicine at 0.4 micrograms/ml, termed GH4C1/RC.4, exhibited the multidrug-resistance phenotype, as the LD50 values for colchicine, puromycin, actinomycin D, and doxorubicin were between 8 and 30 times greater than the corresponding values for the parental GH4C1 cells.Immunocytochemical staining with a monoclonal antibody, C219, to the 170-kilodalton P-glycoprotein showed directly that GH4C1/RC.4 cells overexpress P-glycoprotein.
References
Ref 1 Quantitative Proteomic Profiling Identifies SOX8 as Novel Regulator of Drug Resistance in Gestational Trophoblastic Neoplasia .Front Oncol. 2020 Apr 28;10:557. doi: 10.3389/fonc.2020.00557. eCollection 2020. 10.3389/fonc.2020.00557
Ref 2 Characterization of multidrug-resistant pituitary tumor cells .Endocrinology. 1992 Jun;130(6):3246-56. doi: 10.1210/endo.130.6.1350759. 10.1210/endo.130.6.1350759

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