Disease Information

General Information of the Disease (ID: DIS00210)

• Name: Gestational trophoblastic neoplasia
• ICD: ICD-11: 2C75

Type(s) of Resistant Mechanism of This Disease

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Methotrexate

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]

• Resistant Disease: Gestational trophoblastic neoplasia [ICD-11: 2C75.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Methotrexate
• 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]

• Resistant Disease: Gestational trophoblastic neoplasia [ICD-11: 2C75.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Methotrexate
• 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.

Investigative Drug(s) 1 drug(s) in total

Actinomycin D

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]

• Resistant Disease: Gestational trophoblastic neoplasia [ICD-11: 2C75.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Actinomycin D
• 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]

• Resistant Disease: Gestational trophoblastic neoplasia [ICD-11: 2C75.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Actinomycin D
• 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]

• Resistant Disease: Gestational trophoblastic neoplasia [ICD-11: 2C75.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Actinomycin D
• 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]

• Resistant Disease: Gestational trophoblastic neoplasia [ICD-11: 2C75.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Actinomycin D
• 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.

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