Radiation enhancement by the combined use of topoisomerase I inhibitors, RFS-2000 or CPT-11, and topoisomerase II inhibitor etoposide in human lung cancer cells

Jae Sung Kim, George P. Amorino, Hongryull Pyo, Qianwen Cao, Hak Choy

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background and purpose: We have tested the camptothecin analogs, RFS-2000 or CPT-11, in combination with both etoposide and ionizing radiation in vitro to examine the radiation enhancing potential of topoisomerase I plus topoisomerase II (Topo I + Topo II) inhibition in human cancer cells. Materials and methods: H460 human lung carcinoma cells were plated and treated with 10 nM RFS-2000 or 4.5 μM CPT-11 for 4 h. Cells were then irradiated with various doses and treated with 1 μM etoposide for 1.5 h. Cell survival and sublethal damage recovery (SLDR) were determined by clonogenic assay. 7-aminoactinomycin D (7-AAD) staining and flow cytometry were used to analyze cell viability/apoptosis after combined treatment of drugs with radiation. Results: Survival experiments showed radiation dose enhancement ratios (DER) of 1.26, 1.34, and 1.63 for RFS-2000, etoposide, and RFS-2000 plus etoposide, respectively; the corresponding DER values were 1.30, 1.39, and 1.65 for CPT-11, etoposide, and CPT-11 plus etoposide. The analysis of cell viability/apoptosis using 7-AAD staining and flow cytometry showed an additive effect. Greater inhibition of SLDR was observed with RFS-2000 plus etoposide than with either agent separately, but CPT-11 plus etoposide showed a more modest effect upon SLDR. Conclusions: These data show that the combination of Topo I inhibitors, RFS-2000 or CPT-11 plus Topo II inhibitor etoposide, is a more effective radiation enhancer than either agent alone in human lung cancer cells. The mechanism of radiation enhancement may involve inhibition of SLDR with RFS-2000 plus etoposide, but other mechanisms may be involved in the combined treatment including CPT-11.

Original languageEnglish (US)
Pages (from-to)61-67
Number of pages7
JournalRadiotherapy and Oncology
Volume62
Issue number1
DOIs
StatePublished - 2002

Fingerprint

irinotecan
Topoisomerase I Inhibitors
Topoisomerase II Inhibitors
Carnitine O-Palmitoyltransferase
Etoposide
Lung Neoplasms
Radiation
Cell Survival
Flow Cytometry
rubitecan
Apoptosis
Staining and Labeling
Camptothecin
Type II DNA Topoisomerase
Type I DNA Topoisomerase

Keywords

  • CPT-11
  • Etoposide
  • Lung cancer
  • Radiation
  • RFS-2000

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Urology

Cite this

Radiation enhancement by the combined use of topoisomerase I inhibitors, RFS-2000 or CPT-11, and topoisomerase II inhibitor etoposide in human lung cancer cells. / Kim, Jae Sung; Amorino, George P.; Pyo, Hongryull; Cao, Qianwen; Choy, Hak.

In: Radiotherapy and Oncology, Vol. 62, No. 1, 2002, p. 61-67.

Research output: Contribution to journalArticle

@article{95e78b64c56646008cfc2df00f30602e,
title = "Radiation enhancement by the combined use of topoisomerase I inhibitors, RFS-2000 or CPT-11, and topoisomerase II inhibitor etoposide in human lung cancer cells",
abstract = "Background and purpose: We have tested the camptothecin analogs, RFS-2000 or CPT-11, in combination with both etoposide and ionizing radiation in vitro to examine the radiation enhancing potential of topoisomerase I plus topoisomerase II (Topo I + Topo II) inhibition in human cancer cells. Materials and methods: H460 human lung carcinoma cells were plated and treated with 10 nM RFS-2000 or 4.5 μM CPT-11 for 4 h. Cells were then irradiated with various doses and treated with 1 μM etoposide for 1.5 h. Cell survival and sublethal damage recovery (SLDR) were determined by clonogenic assay. 7-aminoactinomycin D (7-AAD) staining and flow cytometry were used to analyze cell viability/apoptosis after combined treatment of drugs with radiation. Results: Survival experiments showed radiation dose enhancement ratios (DER) of 1.26, 1.34, and 1.63 for RFS-2000, etoposide, and RFS-2000 plus etoposide, respectively; the corresponding DER values were 1.30, 1.39, and 1.65 for CPT-11, etoposide, and CPT-11 plus etoposide. The analysis of cell viability/apoptosis using 7-AAD staining and flow cytometry showed an additive effect. Greater inhibition of SLDR was observed with RFS-2000 plus etoposide than with either agent separately, but CPT-11 plus etoposide showed a more modest effect upon SLDR. Conclusions: These data show that the combination of Topo I inhibitors, RFS-2000 or CPT-11 plus Topo II inhibitor etoposide, is a more effective radiation enhancer than either agent alone in human lung cancer cells. The mechanism of radiation enhancement may involve inhibition of SLDR with RFS-2000 plus etoposide, but other mechanisms may be involved in the combined treatment including CPT-11.",
keywords = "CPT-11, Etoposide, Lung cancer, Radiation, RFS-2000",
author = "Kim, {Jae Sung} and Amorino, {George P.} and Hongryull Pyo and Qianwen Cao and Hak Choy",
year = "2002",
doi = "10.1016/S0167-8140(01)00465-0",
language = "English (US)",
volume = "62",
pages = "61--67",
journal = "Radiotherapy and Oncology",
issn = "0167-8140",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - Radiation enhancement by the combined use of topoisomerase I inhibitors, RFS-2000 or CPT-11, and topoisomerase II inhibitor etoposide in human lung cancer cells

AU - Kim, Jae Sung

AU - Amorino, George P.

AU - Pyo, Hongryull

AU - Cao, Qianwen

AU - Choy, Hak

PY - 2002

Y1 - 2002

N2 - Background and purpose: We have tested the camptothecin analogs, RFS-2000 or CPT-11, in combination with both etoposide and ionizing radiation in vitro to examine the radiation enhancing potential of topoisomerase I plus topoisomerase II (Topo I + Topo II) inhibition in human cancer cells. Materials and methods: H460 human lung carcinoma cells were plated and treated with 10 nM RFS-2000 or 4.5 μM CPT-11 for 4 h. Cells were then irradiated with various doses and treated with 1 μM etoposide for 1.5 h. Cell survival and sublethal damage recovery (SLDR) were determined by clonogenic assay. 7-aminoactinomycin D (7-AAD) staining and flow cytometry were used to analyze cell viability/apoptosis after combined treatment of drugs with radiation. Results: Survival experiments showed radiation dose enhancement ratios (DER) of 1.26, 1.34, and 1.63 for RFS-2000, etoposide, and RFS-2000 plus etoposide, respectively; the corresponding DER values were 1.30, 1.39, and 1.65 for CPT-11, etoposide, and CPT-11 plus etoposide. The analysis of cell viability/apoptosis using 7-AAD staining and flow cytometry showed an additive effect. Greater inhibition of SLDR was observed with RFS-2000 plus etoposide than with either agent separately, but CPT-11 plus etoposide showed a more modest effect upon SLDR. Conclusions: These data show that the combination of Topo I inhibitors, RFS-2000 or CPT-11 plus Topo II inhibitor etoposide, is a more effective radiation enhancer than either agent alone in human lung cancer cells. The mechanism of radiation enhancement may involve inhibition of SLDR with RFS-2000 plus etoposide, but other mechanisms may be involved in the combined treatment including CPT-11.

AB - Background and purpose: We have tested the camptothecin analogs, RFS-2000 or CPT-11, in combination with both etoposide and ionizing radiation in vitro to examine the radiation enhancing potential of topoisomerase I plus topoisomerase II (Topo I + Topo II) inhibition in human cancer cells. Materials and methods: H460 human lung carcinoma cells were plated and treated with 10 nM RFS-2000 or 4.5 μM CPT-11 for 4 h. Cells were then irradiated with various doses and treated with 1 μM etoposide for 1.5 h. Cell survival and sublethal damage recovery (SLDR) were determined by clonogenic assay. 7-aminoactinomycin D (7-AAD) staining and flow cytometry were used to analyze cell viability/apoptosis after combined treatment of drugs with radiation. Results: Survival experiments showed radiation dose enhancement ratios (DER) of 1.26, 1.34, and 1.63 for RFS-2000, etoposide, and RFS-2000 plus etoposide, respectively; the corresponding DER values were 1.30, 1.39, and 1.65 for CPT-11, etoposide, and CPT-11 plus etoposide. The analysis of cell viability/apoptosis using 7-AAD staining and flow cytometry showed an additive effect. Greater inhibition of SLDR was observed with RFS-2000 plus etoposide than with either agent separately, but CPT-11 plus etoposide showed a more modest effect upon SLDR. Conclusions: These data show that the combination of Topo I inhibitors, RFS-2000 or CPT-11 plus Topo II inhibitor etoposide, is a more effective radiation enhancer than either agent alone in human lung cancer cells. The mechanism of radiation enhancement may involve inhibition of SLDR with RFS-2000 plus etoposide, but other mechanisms may be involved in the combined treatment including CPT-11.

KW - CPT-11

KW - Etoposide

KW - Lung cancer

KW - Radiation

KW - RFS-2000

UR - http://www.scopus.com/inward/record.url?scp=0036159856&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036159856&partnerID=8YFLogxK

U2 - 10.1016/S0167-8140(01)00465-0

DO - 10.1016/S0167-8140(01)00465-0

M3 - Article

C2 - 11830313

AN - SCOPUS:0036159856

VL - 62

SP - 61

EP - 67

JO - Radiotherapy and Oncology

JF - Radiotherapy and Oncology

SN - 0167-8140

IS - 1

ER -