Abstract
Lung-tumor cells from pleural effusion of four refractory patients and in cell lines established from them were analyzed for anthracycline retention, cytotoxicity, and MDR-1 gene and P-glycoprotein expression. Murine leukemic P388 and doxorubicin-resistant P388/R84 lines were used as controls. The 50% growth-inhibitory concentration (IC50) for doxorubicin among lung-tumor lines varied from 0.16 to 0.31 μM in soft agar. Heterogeneity in doxorubicin or daunorubicin retention and response to the efflux-blocking action of 25 μm prochlorperazine was noted in pleural effusion of FCCL-1,-4, and-8. Among the cell lines established, an efflux-blocking effect in a subpopulation was noticed only in FCCL-1 and-4. Although the MDR-1 gene was present in all cell lines, including P388, its expression was pronounced only in P388/R84 and FCCL-1. In situ hybridization of antisense RNA probe to tumor cells showed high heterogeneity for MDR-1 message in the human lung-tumor cells as compared with the murine cells. Northern and slot blot hybridization confirmed in situ hybridization in lines with high levels of MDR-1 expression. The synthesis of MDR-1 mRNA and P-glycoprotein in tumor lines was correlated. The results suggest that because of extensive tumor-cell heterogeneity in human tumors, monitoring of MDR expression by in situ hybridization, quantitation of P0glycoprotein content by laser flow cytometry (and/or immunohistochemical methods), and drug efflux (by laser flow cytometry) may be the best ways to monitor multidrug resistance in human tumors.
| Original language | English |
|---|---|
| Pages (from-to) | 431-441 |
| Number of pages | 11 |
| Journal | Cancer Chemotherapy and Pharmacology |
| Volume | 31 |
| Issue number | 6 |
| DOIs | |
| State | Published - Nov 1 1993 |
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ASJC Scopus subject areas
- Pharmacology
- Oncology
- Cancer Research
Cite this
MDR-1 gene expression, anthracycline retention and cytotoxicity in human lung-tumor cells from refractory patients. / Ramachandran, Cheppail; Sauerteig, Antonieta; Sridhar, Kasi S.; Thurer, Richard J; Krishan, Awtar.
In: Cancer Chemotherapy and Pharmacology, Vol. 31, No. 6, 01.11.1993, p. 431-441.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MDR-1 gene expression, anthracycline retention and cytotoxicity in human lung-tumor cells from refractory patients
AU - Ramachandran, Cheppail
AU - Sauerteig, Antonieta
AU - Sridhar, Kasi S.
AU - Thurer, Richard J
AU - Krishan, Awtar
PY - 1993/11/1
Y1 - 1993/11/1
N2 - Lung-tumor cells from pleural effusion of four refractory patients and in cell lines established from them were analyzed for anthracycline retention, cytotoxicity, and MDR-1 gene and P-glycoprotein expression. Murine leukemic P388 and doxorubicin-resistant P388/R84 lines were used as controls. The 50% growth-inhibitory concentration (IC50) for doxorubicin among lung-tumor lines varied from 0.16 to 0.31 μM in soft agar. Heterogeneity in doxorubicin or daunorubicin retention and response to the efflux-blocking action of 25 μm prochlorperazine was noted in pleural effusion of FCCL-1,-4, and-8. Among the cell lines established, an efflux-blocking effect in a subpopulation was noticed only in FCCL-1 and-4. Although the MDR-1 gene was present in all cell lines, including P388, its expression was pronounced only in P388/R84 and FCCL-1. In situ hybridization of antisense RNA probe to tumor cells showed high heterogeneity for MDR-1 message in the human lung-tumor cells as compared with the murine cells. Northern and slot blot hybridization confirmed in situ hybridization in lines with high levels of MDR-1 expression. The synthesis of MDR-1 mRNA and P-glycoprotein in tumor lines was correlated. The results suggest that because of extensive tumor-cell heterogeneity in human tumors, monitoring of MDR expression by in situ hybridization, quantitation of P0glycoprotein content by laser flow cytometry (and/or immunohistochemical methods), and drug efflux (by laser flow cytometry) may be the best ways to monitor multidrug resistance in human tumors.
AB - Lung-tumor cells from pleural effusion of four refractory patients and in cell lines established from them were analyzed for anthracycline retention, cytotoxicity, and MDR-1 gene and P-glycoprotein expression. Murine leukemic P388 and doxorubicin-resistant P388/R84 lines were used as controls. The 50% growth-inhibitory concentration (IC50) for doxorubicin among lung-tumor lines varied from 0.16 to 0.31 μM in soft agar. Heterogeneity in doxorubicin or daunorubicin retention and response to the efflux-blocking action of 25 μm prochlorperazine was noted in pleural effusion of FCCL-1,-4, and-8. Among the cell lines established, an efflux-blocking effect in a subpopulation was noticed only in FCCL-1 and-4. Although the MDR-1 gene was present in all cell lines, including P388, its expression was pronounced only in P388/R84 and FCCL-1. In situ hybridization of antisense RNA probe to tumor cells showed high heterogeneity for MDR-1 message in the human lung-tumor cells as compared with the murine cells. Northern and slot blot hybridization confirmed in situ hybridization in lines with high levels of MDR-1 expression. The synthesis of MDR-1 mRNA and P-glycoprotein in tumor lines was correlated. The results suggest that because of extensive tumor-cell heterogeneity in human tumors, monitoring of MDR expression by in situ hybridization, quantitation of P0glycoprotein content by laser flow cytometry (and/or immunohistochemical methods), and drug efflux (by laser flow cytometry) may be the best ways to monitor multidrug resistance in human tumors.
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UR - http://www.scopus.com/inward/citedby.url?scp=0027459423&partnerID=8YFLogxK
U2 - 10.1007/BF00685031
DO - 10.1007/BF00685031
M3 - Article
C2 - 8095859
AN - SCOPUS:0027459423
VL - 31
SP - 431
EP - 441
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
SN - 0344-5704
IS - 6
ER -