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[Resistance to anticancer drugs in NIH3T3 cells transfected with c-myc and/or c-H-ras genes]
S Niimi1, S Yokoyama, Y Terashima
1Department of Obstetrics and Gynecology, Jikei University School of Medicine, Tokyo, Japan.
Abstract:
NIH3T3 cells transfected with c-H-ras and/or c-myc genes were examined for differences in drug sensitivity. The two transfectants used were NIH3T3-nm-1 (nm-1), pT22-3-nm-2. They were transfected with c-myc, c-myc plus activated c-H-ras, respectively. The relative resistances (IC50 values of transfectants/those of NIH3T3 cells) to cisplatin, adriamycin, 4-hydroperoxycyclophosphamide, melphalan, and CPT-11 were 2.1, 1.6, 4.7, 4.9, 1.6, respectively for nm-1 and 1.6, 2.2, 3.3, 9.1 and 2.2, respectively for nm-2. These results strongly suggest that the expression of the c-myc gene plays a role for the acquisition of drug resistance. The c-myc gene is believed to provide us an important clue for determining the mechanism of drug resistance.
Insights
The c-myc gene enhances cancer drug resistance in NIH3T3 cells. This finding offers insights into drug resistance mechanisms, potentially improving cancer therapy strategies.
Area of Science:
- Molecular biology
- Cancer research
- Genetics
Context:
- Oncogene expression significantly impacts cellular responses to chemotherapy.
- Understanding the role of specific oncogenes like c-myc in drug resistance is crucial for developing effective cancer treatments.
Purpose:
- To investigate the influence of c-myc gene expression on the drug sensitivity of NIH3T3 cells.
- To determine if co-expression of c-myc and c-H-ras further modifies drug resistance profiles.
Summary:
- NIH3T3 cells transfected with c-myc (nm-1) and c-myc plus c-H-ras (nm-2) were assessed for resistance to cisplatin, adriamycin, 4-hydroperoxycyclophosphamide, melphalan, and CPT-11.
- nm-1 cells showed increased resistance to several agents, with notable fold-changes for 4-hydroperoxycyclophosphamide (4.7) and melphalan (4.9).
- nm-2 cells exhibited heightened resistance, particularly to melphalan (9.1-fold), suggesting a complex interplay between c-myc and c-H-ras in modulating drug sensitivity.
Impact:
- The study strongly suggests that c-myc gene expression is a key factor in the development of drug resistance.
- These findings provide a critical clue for elucidating the molecular mechanisms underlying cancer drug resistance.
- This research may pave the way for novel therapeutic strategies targeting drug-resistant cancers.