Drug Information

Drug (ID: DG00597) and It's Reported Resistant Information

• Name: Actinomycin D
• Synonyms: Etoposide; Methotrexate; Actinomycin D; Cyclophosphamide; Vincristine
• 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]
• 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

Gestational trophoblastic neoplasia [ICD-11: 2C75]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: SRY-box transcription factor 8 (SOX8) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Gestational trophoblastic neoplasia [ICD-11: 2C75.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: 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
• Resistant Disease: Gestational trophoblastic neoplasia [ICD-11: 2C75.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: 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
• Resistant Disease: Gestational trophoblastic neoplasia [ICD-11: 2C75.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: 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
• Resistant Disease: Gestational trophoblastic neoplasia [ICD-11: 2C75.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: 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]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [2]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Pituitary adenoma [ICD-11: 2F37.1]
• 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