Establishment of new multidrug-resistant human osteosarcoma cell lines

Yoshinao Oda, Yoshihiro Matsumoto, Katsumi Harimaya, Yukihide Iwamoto, Masazumi Tsuneyoshi

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Multidrug-resistant clones of human osteosarcoma MNNG/HOS and MG63 cells were isolated by stepwise selection on exposure to increasing doses of doxorubicin (DXR). The final clones MNNG/HOS/DXR1000 and MG63/DXR1000, established after ethylmethane sulfonate mutagenesis, showed 96-fold and 121-fold higer resistance to DXR than their parental cell lines. They were also cross-resistant to vincristine, but not to cisplatinum or methotrexate. The levels of multidrug-resistance-1 (MDR1) mRNA expression increased gradually according to the concentration of DXR in both cell lines. Although the parental MNNG/ HOS cells expressed a low level of MDR1 mRNA, the parental MG63 cells showed no MDR1 expression. The IC50 values of MNNG/HOS and its resistant variant to DXR were higher than those of MG63 and its resistant clone. Multidrug-resistant associated protein (MRP) mRNA expression was detected in MNNG/HOS or MG63 parental cell lines, and in their resistant variants. MG63 and its resistant variants revealed stable expression of MRP, whereas the resistant phenotype of MNNG/HOS showed decreased MRP expression, compared to its parental cell line. No alteration in the levels of hepatocyte growth factor (HGF) or its receptor c-MET was recognized between parental lines and their resistant variants. The results indicate that our DXR-resistant variants of MNNG/HOS and MG63 reveal a classical MDR phenotype and can offer a model with which to investigate the mechanisms of multidrug resistance in osteosarcoma.

Original languageEnglish
Pages (from-to)859-866
Number of pages8
JournalOncology Reports
Volume7
Issue number4
Publication statusPublished - Jan 1 2000

Fingerprint

Methylnitronitrosoguanidine
Osteosarcoma
Doxorubicin
Cell Line
Multiple Drug Resistance
Clone Cells
Messenger RNA
Ethyl Methanesulfonate
Phenotype
Proteins
Hepatocyte Growth Factor
Vincristine
Methotrexate
Mutagenesis
Inhibitory Concentration 50

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Establishment of new multidrug-resistant human osteosarcoma cell lines. / Oda, Yoshinao; Matsumoto, Yoshihiro; Harimaya, Katsumi; Iwamoto, Yukihide; Tsuneyoshi, Masazumi.

In: Oncology Reports, Vol. 7, No. 4, 01.01.2000, p. 859-866.

Research output: Contribution to journalArticle

@article{44f448cf9fe84cf7adc3974de50ec778,
title = "Establishment of new multidrug-resistant human osteosarcoma cell lines",
abstract = "Multidrug-resistant clones of human osteosarcoma MNNG/HOS and MG63 cells were isolated by stepwise selection on exposure to increasing doses of doxorubicin (DXR). The final clones MNNG/HOS/DXR1000 and MG63/DXR1000, established after ethylmethane sulfonate mutagenesis, showed 96-fold and 121-fold higer resistance to DXR than their parental cell lines. They were also cross-resistant to vincristine, but not to cisplatinum or methotrexate. The levels of multidrug-resistance-1 (MDR1) mRNA expression increased gradually according to the concentration of DXR in both cell lines. Although the parental MNNG/ HOS cells expressed a low level of MDR1 mRNA, the parental MG63 cells showed no MDR1 expression. The IC50 values of MNNG/HOS and its resistant variant to DXR were higher than those of MG63 and its resistant clone. Multidrug-resistant associated protein (MRP) mRNA expression was detected in MNNG/HOS or MG63 parental cell lines, and in their resistant variants. MG63 and its resistant variants revealed stable expression of MRP, whereas the resistant phenotype of MNNG/HOS showed decreased MRP expression, compared to its parental cell line. No alteration in the levels of hepatocyte growth factor (HGF) or its receptor c-MET was recognized between parental lines and their resistant variants. The results indicate that our DXR-resistant variants of MNNG/HOS and MG63 reveal a classical MDR phenotype and can offer a model with which to investigate the mechanisms of multidrug resistance in osteosarcoma.",
author = "Yoshinao Oda and Yoshihiro Matsumoto and Katsumi Harimaya and Yukihide Iwamoto and Masazumi Tsuneyoshi",
year = "2000",
month = "1",
day = "1",
language = "English",
volume = "7",
pages = "859--866",
journal = "Oncology Reports",
issn = "1021-335X",
publisher = "Spandidos Publications",
number = "4",

}

TY - JOUR

T1 - Establishment of new multidrug-resistant human osteosarcoma cell lines

AU - Oda, Yoshinao

AU - Matsumoto, Yoshihiro

AU - Harimaya, Katsumi

AU - Iwamoto, Yukihide

AU - Tsuneyoshi, Masazumi

PY - 2000/1/1

Y1 - 2000/1/1

N2 - Multidrug-resistant clones of human osteosarcoma MNNG/HOS and MG63 cells were isolated by stepwise selection on exposure to increasing doses of doxorubicin (DXR). The final clones MNNG/HOS/DXR1000 and MG63/DXR1000, established after ethylmethane sulfonate mutagenesis, showed 96-fold and 121-fold higer resistance to DXR than their parental cell lines. They were also cross-resistant to vincristine, but not to cisplatinum or methotrexate. The levels of multidrug-resistance-1 (MDR1) mRNA expression increased gradually according to the concentration of DXR in both cell lines. Although the parental MNNG/ HOS cells expressed a low level of MDR1 mRNA, the parental MG63 cells showed no MDR1 expression. The IC50 values of MNNG/HOS and its resistant variant to DXR were higher than those of MG63 and its resistant clone. Multidrug-resistant associated protein (MRP) mRNA expression was detected in MNNG/HOS or MG63 parental cell lines, and in their resistant variants. MG63 and its resistant variants revealed stable expression of MRP, whereas the resistant phenotype of MNNG/HOS showed decreased MRP expression, compared to its parental cell line. No alteration in the levels of hepatocyte growth factor (HGF) or its receptor c-MET was recognized between parental lines and their resistant variants. The results indicate that our DXR-resistant variants of MNNG/HOS and MG63 reveal a classical MDR phenotype and can offer a model with which to investigate the mechanisms of multidrug resistance in osteosarcoma.

AB - Multidrug-resistant clones of human osteosarcoma MNNG/HOS and MG63 cells were isolated by stepwise selection on exposure to increasing doses of doxorubicin (DXR). The final clones MNNG/HOS/DXR1000 and MG63/DXR1000, established after ethylmethane sulfonate mutagenesis, showed 96-fold and 121-fold higer resistance to DXR than their parental cell lines. They were also cross-resistant to vincristine, but not to cisplatinum or methotrexate. The levels of multidrug-resistance-1 (MDR1) mRNA expression increased gradually according to the concentration of DXR in both cell lines. Although the parental MNNG/ HOS cells expressed a low level of MDR1 mRNA, the parental MG63 cells showed no MDR1 expression. The IC50 values of MNNG/HOS and its resistant variant to DXR were higher than those of MG63 and its resistant clone. Multidrug-resistant associated protein (MRP) mRNA expression was detected in MNNG/HOS or MG63 parental cell lines, and in their resistant variants. MG63 and its resistant variants revealed stable expression of MRP, whereas the resistant phenotype of MNNG/HOS showed decreased MRP expression, compared to its parental cell line. No alteration in the levels of hepatocyte growth factor (HGF) or its receptor c-MET was recognized between parental lines and their resistant variants. The results indicate that our DXR-resistant variants of MNNG/HOS and MG63 reveal a classical MDR phenotype and can offer a model with which to investigate the mechanisms of multidrug resistance in osteosarcoma.

UR - http://www.scopus.com/inward/record.url?scp=0034220888&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034220888&partnerID=8YFLogxK

M3 - Article

C2 - 10854558

AN - SCOPUS:0034220888

VL - 7

SP - 859

EP - 866

JO - Oncology Reports

JF - Oncology Reports

SN - 1021-335X

IS - 4

ER -