Related Experiment Video
Updated: Apr 29, 2026
Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
Prevention of multidrug resistance (MDR) in osteosarcoma by NSC23925
11] Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, 100 Blossom Street, Jackson 1115, Boston, MA 02114, USA [2] Department of Gynaecology and Obstetrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
Background:
The major limitation to the success of chemotherapy in osteosarcoma is the development of multidrug resistance (MDR). Preventing the emergence of MDR during chemotherapy treatment has been a high priority of clinical and investigational oncology, but it remains an elusive goal. The NSC23925 has recently been identified as a novel and potent MDR reversal agent. However, whether NSC23925 can prevent the development of MDR in cancer is unknown. Therefore, this study aims to evaluate the effects of NSC23925 on prevention of the development of MDR in osteosarcoma.
Methods:
Human osteosarcoma cell lines U-2OS and Saos were exposed to increasing concentrations of paclitaxel alone or in combination with NSC23925 for 6 months. Cell sublines selected at different time points were evaluated for their drug sensitivity, drug transporter P-glycoprotein (Pgp) expression and activity.
Results:
We observed that tumour cells selected with increasing concentrations of paclitaxel alone developed MDR with resistance to paclitaxel and other Pgp substrates, whereas cells cultured with paclitaxel-NSC23925 did not develop MDR and cells remained sensitive to chemotherapeutic agents. Paclitaxel-resistant cells showed high expression and activity of the Pgp, whereas paclitaxel-NSC23925-treated cells did not express Pgp. No changes in IC50 and Pgp expression and activity were observed in cells grown with the NSC23925 alone.
Conclusions:
Our findings suggest that NSC23925 may prevent the development of MDR by specifically preventing the overexpression of Pgp. Given the significant incidence of MDR in osteosarcoma and the lack of effective agents for prevention of MDR, NSC23925 and derivatives hold the potential to improve the outcome of cancer patients with poor prognosis due to drug resistance.
Insights
The novel agent NSC23925 prevents multidrug resistance (MDR) development in osteosarcoma cells. This study shows NSC23925 inhibits P-glycoprotein (Pgp) overexpression, maintaining chemotherapy sensitivity.
Area of Science:
- Oncology
- Pharmacology
- Cancer Biology
Background:
- Multidrug resistance (MDR) significantly limits osteosarcoma chemotherapy efficacy.
- Preventing MDR emergence during treatment is a critical, yet unmet, clinical need.
- NSC23925 is a newly identified potent MDR reversal agent, but its preventative role is unexplored.
Purpose of the Study:
- To investigate the efficacy of NSC23925 in preventing the development of MDR in osteosarcoma.
- To evaluate NSC23925's impact on drug sensitivity and P-glycoprotein (Pgp) expression in osteosarcoma cells.
Main Methods:
- Human osteosarcoma cell lines (U-2OS, Saos) were treated with paclitaxel alone or with paclitaxel plus NSC23925 for six months.
- Drug sensitivity, P-glycoprotein (Pgp) expression, and Pgp activity were assessed in selected cell sublines at various time points.
Main Results:
- Cells treated with paclitaxel alone developed MDR and resistance to Pgp substrates.
- Co-treatment with paclitaxel and NSC23925 prevented MDR development, maintaining sensitivity to chemotherapeutic agents.
- Paclitaxel-resistant cells exhibited high Pgp expression and activity; NSC23925-treated cells showed no Pgp overexpression or activity.
Conclusions:
- NSC23925 demonstrates potential in preventing MDR by inhibiting Pgp overexpression.
- This finding suggests NSC23925 and its derivatives could improve outcomes for osteosarcoma patients with drug resistance.
- The agent warrants further investigation for its role in overcoming chemotherapy resistance in cancer treatment.
