Molecule Information

General Information of the Molecule (ID: Mol00025)

• Name: Apoptosis regulator BAX (BAX) ,Homo sapiens
• Synonyms: Bcl-2-like protein 4; Bcl2-L-4; BCL2L4
• Molecule Type: Protein
• Gene Name: BAX
• Gene ID: 581
• Location: chr19:48954815-48961798[+]
• Sequence:
  MDGSGEQPRGGGPTSSEQIMKTGALLLQGFIQDRAGRMGGEAPELALDPVPQDASTKKLS
  ECLKRIGDELDSNMELQRMIAAVDTDSPREVFFRVAADMFSDGNFNWGRVVALFYFASKL
  VLKALCTKVPELIRTIMGWTLDFLRERLLGWIQDQGGWDGLLSYFGTPTWQTVTIFVAGV
  LTASLTIWKKMG
• Function: Plays a role in the mitochondrial apoptotic process. Under normal conditions, BAX is largely cytosolic via constant retrotranslocation from mitochondria to the cytosol mediated by BCL2L1/Bcl-xL, which avoids accumulation of toxic BAX levels at the mitochondrial outer membrane (MOM). Under stress conditions, undergoes a conformation change that causes translocation to the mitochondrion membrane, leading to the release of cytochrome c that then triggers apoptosis. Promotes activation of CASP3, and thereby apoptosis.
• Uniprot ID: BAX_HUMAN
• Ensembl ID: ENSG00000087088
• HGNC ID: HGNC:959

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 7 drug(s) in total

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Gastric cancer [1]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: LncRNA SNHG5 promotes cisplatin resistance in gastric cancer via inhibiting cell apoptosis and upregulating drug resistance-related genes.

Disease Class: Bladder cancer [2]

• Resistant Disease: Bladder cancer [ICD-11: 2C94.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: 5637 cells; Bladder; Homo sapiens (Human); CVCL_0126
• In Vitro Model: T24 cells; Bladder; Homo sapiens (Human); CVCL_0554
• In Vitro Model: SW780 cells; Bladder; Homo sapiens (Human); CVCL_1728
• Experiment for Molecule Alteration: Western blot analysis; qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Upregulated HIF1A-AS2 hampers the p53 family proteins dependent apoptotic pathway to promote Cis resistance in bladder cancer.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Non-small cell lung cancer [3]

• Sensitive Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: Sk-MES-1 cells; Lung; Homo sapiens (Human); CVCL_0630
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Down-regulation of miR-21 inhibited growth, colony formation, antiapoptotic Bcl-2 expression and promoted proapoptotic Bax and caspase-9 expression in A549 cells treated with DDP. Upregulation of miR-21 promoted growth and colony formation in Sk-MES-1 cells treated with DDP. Furthermore, downregulation of miR-21 reduced growth of implanted tumors, suggesting that miR-21 inhibition could enhance the sensitivity of A549 cells to DDP in vivo. These data suggest an appropriate combination of DDP and miR-21 regulation might be a potential approach to lung cancer therapy. Combined DDP application with miR-21 downregulation for the treatment of lung cancer would help achieve effective treatment and reduce DDP side effects.

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [4]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• Experiment for Molecule Alteration: Western blot analysis; TUNEL assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Long noncoding RNA LINP1 acts as an oncogene and promotes chemoresistance against 5-fluoroutacil and doxorubicin by inhibiting chemotherapeutics-induced apoptosis (apoptosis-related proteins such as caspase-8, caspase-9 and Bax proteins) in breast cancer.

Disease Class: Breast cancer [5]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• Experiment for Molecule Alteration: luciferase report assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR-128 regulates sensitivity to drugs and apoptosis in breast cancer cells, pro-apoptotic protein bax is negatively post-transcriptionally regulated by miR-128. Bax overexpression could lead to a generalised enhancement of the apoptotic response to death stimuli, miR-128 was significantly associated with a drug fast in breast cancer cells by resisting the activation of the apoptosis pathway.

Etoposide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [5]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Etoposide
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• Experiment for Molecule Alteration: luciferase report assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR-128 regulates sensitivity to drugs and apoptosis in breast cancer cells, pro-apoptotic protein bax is negatively post-transcriptionally regulated by miR-128. Bax overexpression could lead to a generalised enhancement of the apoptotic response to death stimuli, miR-128 was significantly associated with a drug fast in breast cancer cells by resisting the activation of the apoptosis pathway.

Fluorouracil

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [4]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Fluorouracil
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Epithelial mesenchymal transition signaling pathway; Activation; hsa01521
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• Experiment for Molecule Alteration: Western blot analysis; TUNEL assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Long noncoding RNA LINP1 acts as an oncogene and promotes chemoresistance against 5-fluoroutacil and doxorubicin by inhibiting chemotherapeutics-induced apoptosis (apoptosis-related proteins such as caspase-8, caspase-9 and Bax proteins) in breast cancer.

Gemcitabine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Pancreatic cancer [6]

• Resistant Disease: Pancreatic cancer [ICD-11: 2C10.3]
• Resistant Drug: Gemcitabine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: PANC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• In Vitro Model: AsPC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0152
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-365 directly targets the pro-apoptotic molecules SHC1 and BAX, whose reductions contribute to gemcitabine resistance in pancreatic cancer cells.

Paclitaxel

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [7]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Sensitive Drug: Paclitaxel
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: miR-21 inhibitors induced sensitivity of MCF-7/PR and SkBR-3/PR cells to paclitaxel. And miR-21 mimic can increase the expression of MDR1, Bcl-2/Bax and change cell morphology from parental cells to resistant cells.

Stanozolol

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Hereditary angioedema [8]

• Resistant Disease: Hereditary angioedema [ICD-11: 4B05.0]
• Resistant Drug: Stanozolol
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Sprague Dawley male rats model; Rattus norvegicus
• Experiment for Molecule Alteration: Gene expression analysis
• Mechanism Description: Stanozolol can increases levels of Bax, Bcl-2, P53, caspase 3 and Bax/Bcl-2 ratio. Resistance training, 50 and 100 mg/kg Tribulus terrestris and resistance training along with Tribulus terrestris can decrease the Bax, Bcl-2, P53, caspase 3 and Bax/Bcl-2 ratio in rats exposed to Stanozolol.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Gastric cancer [ICD-11: 2B72]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Gastric tissue
• The Specified Disease: Gastric cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.20E-01; Fold-change: 1.97E+00; Z-score: 1.70E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 2.69E-01; Fold-change: 1.80E-01; Z-score: 3.68E-01

Pancreatic cancer [ICD-11: 2C10]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Pancreas
• The Specified Disease: Pancreatic cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.08E-06; Fold-change: 1.50E+00; Z-score: 2.17E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.21E-01; Fold-change: 5.80E-01; Z-score: 6.00E-01

Lung cancer [ICD-11: 2C25]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Lung
• The Specified Disease: Lung cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 8.26E-07; Fold-change: 3.70E-01; Z-score: 6.37E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 4.78E-16; Fold-change: 8.32E-01; Z-score: 1.19E+00

Breast cancer [ICD-11: 2C60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Breast tissue
• The Specified Disease: Breast cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.35E-90; Fold-change: 1.24E+00; Z-score: 2.14E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.27E-07; Fold-change: 7.95E-01; Z-score: 9.70E-01

Bladder cancer [ICD-11: 2C94]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Bladder tissue
• The Specified Disease: Bladder cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.06E-02; Fold-change: -6.27E-01; Z-score: -1.54E+00

References

• Ref 1: LncRNA SNHG5 promotes cisplatin resistance in gastric cancer via inhibiting cell apoptosis. Eur Rev Med Pharmacol Sci. 2019 May;23(10):4185-4191. doi: 10.26355/eurrev_201905_17921.
• Ref 2: The long noncoding RNA HIF1A-AS2 facilitates cisplatin resistance in bladder cancer. J Cell Biochem. 2019 Jan;120(1):243-252. doi: 10.1002/jcb.27327. Epub 2018 Sep 14.
• Ref 3: Downregulation of miR-21 increases cisplatin sensitivity of non-small-cell lung cancer. Cancer Genet. 2014 May;207(5):214-20. doi: 10.1016/j.cancergen.2014.04.003. Epub 2014 Apr 13.
• Ref 4: Long noncoding RNA LINP1 acts as an oncogene and promotes chemoresistance in breast cancer. Cancer Biol Ther. 2018 Feb 1;19(2):120-131. doi: 10.1080/15384047.2017.1394543. Epub 2018 Jan 2.
• Ref 5: Downregulation of miRNA-128 sensitises breast cancer cell to chemodrugs by targeting Bax. Cell Biol Int. 2013 Jul;37(7):653-8. doi: 10.1002/cbin.10100. Epub 2013 May 8.
• Ref 6: MiR-365 induces gemcitabine resistance in pancreatic cancer cells by targeting the adaptor protein SHC1 and pro-apoptotic regulator BAX. Cell Signal. 2014 Feb;26(2):179-85. doi: 10.1016/j.cellsig.2013.11.003. Epub 2013 Nov 9.
• Ref 7: [Effects of miRNA-21 on paclitaxel-resistance in human breast cancer cells]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2015 Jul;44(4):400-9. doi: 10.3785/j.issn.1008-9292.2015.07.09.
• Ref 8: Anti-Apoptotic Effects of Resistance Training and Tribulus Terrestris Consumption in the Heart Tissue of Rats Exposed to Stanozolol .Eurasian J Med. 2021 Jun;53(2):79-84. doi: 10.5152/eurasianjmed.2021.20051. 10.5152/eurasianjmed.2021.20051