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MGr1-Ag/37LRP induces cell adhesion-mediated drug resistance through FAK/PI3K and MAPK pathway in gastric cancer.

Sun L, Liu L, Liu X, Wang Y, Li M, Yao L, Yang J, Ji G, Guo C, Pan Y, Liang S, Wang B, Ding J, Zhang H, Shi Y - Cancer Sci. (2014)

Bottom Line: However, the MGr1-Ag-initiated intracellular signal transduction pathway is still unknown.Further study found that, as a receptor of ECM components, MGr1-Ag/37LRP may activate the downstream signal pathway PI3K/AKT and MAPK/ERK through interaction with phosphorylated FAK.Moreover, the sensitivity to chemotherapeutic drugs could be significantly enhanced by inhibiting MGr1-Ag/37LRP expression through mAbs, siRNA, and antisense oligonucleotide.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.

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Related in: MedlinePlus

Role of Bcl-2 on the cell adhesion-mediated drug resistance phenotype in gastric cancer (GC) MDR variants cells. (a) Cell adhesion assay. After 2 h of adhesion, the cells attached to laminin (LN) and BSA were counted under a microscope. (b) Expression of Bcl-2 in SGC7901 cells in the condition of adhesion to LN (1 μg/cm2) and BSA (0.4 μg/cm2) was evaluated by Western blot. β-Actin was used as an internal control. (c) Apoptosis indexes of GC cells induced by vincristine (VCR) detected by flow cytometry. *P < 0.05 versus SGC7901 adhesion to LN; #P < 0.05 versus SGC7901/VCR and SGC7901/adriamycin (ADR) cell adhesion to BSA control. Representative experiments are shown from three for each cell type.
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fig01: Role of Bcl-2 on the cell adhesion-mediated drug resistance phenotype in gastric cancer (GC) MDR variants cells. (a) Cell adhesion assay. After 2 h of adhesion, the cells attached to laminin (LN) and BSA were counted under a microscope. (b) Expression of Bcl-2 in SGC7901 cells in the condition of adhesion to LN (1 μg/cm2) and BSA (0.4 μg/cm2) was evaluated by Western blot. β-Actin was used as an internal control. (c) Apoptosis indexes of GC cells induced by vincristine (VCR) detected by flow cytometry. *P < 0.05 versus SGC7901 adhesion to LN; #P < 0.05 versus SGC7901/VCR and SGC7901/adriamycin (ADR) cell adhesion to BSA control. Representative experiments are shown from three for each cell type.

Mentions: We previously reported that MGr1-Ag could prompt cell adhesion-mediated GC drug resistance through interaction with LN. It was reported that integrins mediated CAM-DR by upregulation of antiapoptotic Bcl-2.19 To gain insight into the mechanism of MGr1-Ag in CAM-DR, we first examined the adhesive potential of three GC cell lines, including two MDR GC cell lines SGC7901/VCR and SGC7901/adriamycin (ADR), as well as drug-sensitive cell line SGC7901, to LN. As shown in Figure1(a), SGC7901/VCR and SGC7901/ADR showed high adhesive potential to LN, whereas SGC7901 showed relatively low adhesive potential (Fig.1a). Next, we tested the Bcl-2 expression in GC cell lines adhesion to LN and control BSA. Western blot analysis revealed that the expression of Bcl-2 was increased in SGC7901/VCR and SGC7901/ADR cell lines' adhesion to LN than that of SGC7901 adhesion to LN and the two cell lines' adhesion to control BSA (Fig.1b). The annexin V–propidium iodide assay revealed that SGC7901/VCR and SGC7901/ADR cells, after adhesion to ECM components, showed significantly decreased apoptosis index values compared to that of control (Fig.1c). These results suggested that GC MDR cell lines mediated CAM-DR through upregulation of Bcl-2.


MGr1-Ag/37LRP induces cell adhesion-mediated drug resistance through FAK/PI3K and MAPK pathway in gastric cancer.

Sun L, Liu L, Liu X, Wang Y, Li M, Yao L, Yang J, Ji G, Guo C, Pan Y, Liang S, Wang B, Ding J, Zhang H, Shi Y - Cancer Sci. (2014)

Role of Bcl-2 on the cell adhesion-mediated drug resistance phenotype in gastric cancer (GC) MDR variants cells. (a) Cell adhesion assay. After 2 h of adhesion, the cells attached to laminin (LN) and BSA were counted under a microscope. (b) Expression of Bcl-2 in SGC7901 cells in the condition of adhesion to LN (1 μg/cm2) and BSA (0.4 μg/cm2) was evaluated by Western blot. β-Actin was used as an internal control. (c) Apoptosis indexes of GC cells induced by vincristine (VCR) detected by flow cytometry. *P < 0.05 versus SGC7901 adhesion to LN; #P < 0.05 versus SGC7901/VCR and SGC7901/adriamycin (ADR) cell adhesion to BSA control. Representative experiments are shown from three for each cell type.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317895&req=5

fig01: Role of Bcl-2 on the cell adhesion-mediated drug resistance phenotype in gastric cancer (GC) MDR variants cells. (a) Cell adhesion assay. After 2 h of adhesion, the cells attached to laminin (LN) and BSA were counted under a microscope. (b) Expression of Bcl-2 in SGC7901 cells in the condition of adhesion to LN (1 μg/cm2) and BSA (0.4 μg/cm2) was evaluated by Western blot. β-Actin was used as an internal control. (c) Apoptosis indexes of GC cells induced by vincristine (VCR) detected by flow cytometry. *P < 0.05 versus SGC7901 adhesion to LN; #P < 0.05 versus SGC7901/VCR and SGC7901/adriamycin (ADR) cell adhesion to BSA control. Representative experiments are shown from three for each cell type.
Mentions: We previously reported that MGr1-Ag could prompt cell adhesion-mediated GC drug resistance through interaction with LN. It was reported that integrins mediated CAM-DR by upregulation of antiapoptotic Bcl-2.19 To gain insight into the mechanism of MGr1-Ag in CAM-DR, we first examined the adhesive potential of three GC cell lines, including two MDR GC cell lines SGC7901/VCR and SGC7901/adriamycin (ADR), as well as drug-sensitive cell line SGC7901, to LN. As shown in Figure1(a), SGC7901/VCR and SGC7901/ADR showed high adhesive potential to LN, whereas SGC7901 showed relatively low adhesive potential (Fig.1a). Next, we tested the Bcl-2 expression in GC cell lines adhesion to LN and control BSA. Western blot analysis revealed that the expression of Bcl-2 was increased in SGC7901/VCR and SGC7901/ADR cell lines' adhesion to LN than that of SGC7901 adhesion to LN and the two cell lines' adhesion to control BSA (Fig.1b). The annexin V–propidium iodide assay revealed that SGC7901/VCR and SGC7901/ADR cells, after adhesion to ECM components, showed significantly decreased apoptosis index values compared to that of control (Fig.1c). These results suggested that GC MDR cell lines mediated CAM-DR through upregulation of Bcl-2.

Bottom Line: However, the MGr1-Ag-initiated intracellular signal transduction pathway is still unknown.Further study found that, as a receptor of ECM components, MGr1-Ag/37LRP may activate the downstream signal pathway PI3K/AKT and MAPK/ERK through interaction with phosphorylated FAK.Moreover, the sensitivity to chemotherapeutic drugs could be significantly enhanced by inhibiting MGr1-Ag/37LRP expression through mAbs, siRNA, and antisense oligonucleotide.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.

Show MeSH
Related in: MedlinePlus