Related Experiment Video
Updated: Aug 4, 2026
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Selenium (Se) cytotoxicity in drug sensitive and drug resistant murine tumour
Abstract:
Selenium is known to inhibit growth rate of neoplastic cells. We have investigated the role of selenium (Se) in resensitization of the adriamycin (ADR) resistant murine P388/ADR cells to the action of ADR. The experiments were performed in the ADR sensitive parental P388 murine leukemia (P388/S) and its subline P388/ADR, resistant to ADR, developed in our laboratory. The effect of Se was observed to be dose dependent i.e. Se at a concentration of 5 x 10(-8)M resulted in potentiation of DNA biosynthesis whereas 5 x 10(-6)M and 5 x 10(-5)M Se resulted in inhibition of DNA-biosynthesis in P388/S cells. Along with ADR there was a further increase in inhibition of DNA biosynthesis. In P388/ADR cells, Se at 5 x 10(-6)M and 5 x 10(-8)M concentration resulted in inhibition of DNA biosynthesis, which increased further when combined with ADR indicating resensitization of these cells to the action of ADR. The inhibition was observed to be partially irreversible. These results were further confirmed in the in vivo and in vitro bioassays where the Se and Se+ ADR treatments resulted in increased lifespan of tumor bearing mice.
Insights
Selenium (Se) resensitizes adriamycin-resistant cancer cells to chemotherapy. This study shows Se combined with adriamycin (ADR) increases cancer cell death and extends survival in tumor-bearing mice.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Selenium (Se) is recognized for its ability to inhibit neoplastic cell growth.
- Adriamycin (ADR) resistance is a significant challenge in cancer chemotherapy.
- Understanding agents that can overcome drug resistance is crucial for improving treatment outcomes.
Purpose of the Study:
- To investigate the role of selenium (Se) in resensitizing adriamycin (ADR)-resistant murine P388/ADR cells to ADR.
- To evaluate the dose-dependent effects of Se on DNA biosynthesis in both sensitive and resistant cell lines.
- To assess the combined efficacy of Se and ADR in vitro and in vivo.
Main Methods:
- Experiments were conducted using ADR-sensitive P388/S and ADR-resistant P388/ADR murine leukemia cell lines.
- The effect of varying Se concentrations (5 x 10(-8)M, 5 x 10(-6)M, 5 x 10(-5)M) on DNA biosynthesis was measured.
- Cells were treated with Se alone, ADR alone, or a combination of Se and ADR.
- In vivo and in vitro bioassays were performed to confirm findings and assess lifespan in tumor-bearing mice.
Main Results:
- In P388/S cells, Se showed a dose-dependent effect: potentiation of DNA biosynthesis at 5 x 10(-8)M and inhibition at higher concentrations (5 x 10(-6)M, 5 x 10(-5)M).
- In P388/ADR cells, Se (at 5 x 10(-6)M and 5 x 10(-8)M) inhibited DNA biosynthesis, with further significant inhibition when combined with ADR, indicating resensitization.
- The observed inhibition of DNA biosynthesis in resistant cells was partially irreversible.
- Se and Se+ADR treatments significantly increased the lifespan of tumor-bearing mice in bioassays.
Conclusions:
- Selenium resensitizes adriamycin-resistant leukemia cells to adriamycin's cytotoxic effects.
- Combined treatment with selenium and adriamycin demonstrates enhanced efficacy in inhibiting cancer cell growth and improving survival.
- Selenium holds potential as an adjuvant therapy to overcome adriamycin resistance in cancer treatment.
