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Updated: Feb 25, 2026
3-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer
Published on: September 13, 2018
SOCS3 overexpression enhances ADM resistance in bladder cancer T24 cells
1Department of Urology, The Third Affiliated Hospital Sun Yat-Sen University, Guangzhou, Guangdong, China. jiesitu668@163.com.
Objective:
JAK-STAT3 signaling pathway widely participates in cell proliferation and apoptosis. Suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of JAK-STAT3. SOCS3 downregulation is associated with drug resistance in breast cancer and leukemia. However, its role in bladder cancer drug resistance is still unclear. This study established ADM resistant bladder cancer cell model to investigate the role of SOCS3-JAK/STAT3 signaling pathway ADM resistance.
Materials And Methods:
ADM drug resistant cell line T24/ADM was established. SOCS3, p-JAK2, p-JAK3, and Bcl-2 expressions in T24/ADM, T24, and HBEC cells were compared. Cell proliferation and apoptosis were evaluated by flow cytometry. T24/ADM cells were divided into five groups, including control, pSicoR-blank, pSicoR-SOCS3, FLLL32, and pSicoR-SOCS3 + FLLL32 groups. Cell proliferation was determined by EdU staining.
Results:
SOCS3 was reduced, while p-JAK2, p-STAT3, and Bcl-2 expressions upregulated in T24 cells compared with HBEC cells. T24/ADM cells exhibited lower SOCS3, higher p-JAK2, p-STAT3, and Bcl-2 levels than T24 cells. Cell apoptosis was higher, whereas cell proliferation was weaker in T24 cells compared with T24/ADM cells. SOCS3 overexpression and/or FLLL32 treatment significantly downregulated p-JAK2, p-STAT3, and Bcl-2 expressions, attenuated cell proliferation, and elevated sensitivity to ADM induced cell apoptosis.
Conclusions:
SOCS3 reduction was associated with bladder cancer sensitivity to ADM. SOCS3 overexpression decreased JAK-STAT3 signaling pathway activity, declined Bcl-2 expression, inhibited cell proliferation, elevated cell apoptosis, and enhanced ADM sensitivity in T24 cells.
Insights
Suppressor of cytokine signaling 3 (SOCS3) reduction is linked to bladder cancer resistance to ADM. Restoring SOCS3 enhances ADM sensitivity by inhibiting the JAK/STAT3 pathway and promoting apoptosis.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The JAK-STAT3 pathway regulates cell proliferation and apoptosis.
- Suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of JAK-STAT3.
- SOCS3 downregulation is implicated in drug resistance in various cancers, but its role in bladder cancer remains unclear.
Purpose of the Study:
- To investigate the role of the SOCS3-JAK/STAT3 signaling pathway in Adriamycin (ADM) resistance in bladder cancer.
- To establish an ADM-resistant bladder cancer cell model for studying SOCS3 function.
Main Methods:
- Established an ADM-resistant bladder cancer cell line (T24/ADM).
- Compared SOCS3, p-JAK2, p-JAK3, and Bcl-2 expression in T24/ADM, T24, and normal HBEC cells.
- Assessed cell proliferation and apoptosis using flow cytometry and EdU staining.
- Investigated the effects of SOCS3 overexpression and FLLL32 treatment on T24/ADM cells.
Main Results:
- T24/ADM cells showed reduced SOCS3 and increased p-JAK2, p-STAT3, and Bcl-2 compared to T24 cells.
- T24 cells exhibited higher apoptosis and lower proliferation than T24/ADM cells.
- SOCS3 overexpression and/or FLLL32 treatment decreased p-JAK2, p-STAT3, and Bcl-2, reduced proliferation, and enhanced ADM-induced apoptosis.
Conclusions:
- SOCS3 downregulation is associated with bladder cancer resistance to ADM.
- Overexpression of SOCS3 inhibits the JAK-STAT3 pathway, reduces Bcl-2, suppresses proliferation, and increases apoptosis.
- Restoring SOCS3 enhances bladder cancer cell sensitivity to ADM.
