Combination Effect between Bortezomib and Tumor Necrosis Factor α on Gefitinib-resistant Non-small Cell Lung Cancer Cell Lines
Tumor cells that have acquired resistance to gefitinib may complicate the future treatment of patients with non-small cell lung cancer (NSCLC). To investigate the mechanisms of acquired resistance, an acquired gefitinib-resistant cell line, PC-9/ZD2001, has been established using a gefitinib-sensiti...
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| Veröffentlicht in: | Anticancer research 2009-06, Vol.29 (6), p.2315 |
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| creator | SOJIRO KUSUMOTO TOMOHIDE SUGIYAMA KOICHI ANDO TAKAMICHI HOSAKA HIROO ISHIDA TAKAO SHIRAI TOSHIMITSU YAMAOKA KENTARO OKUDA TAKASHI HIROSE TSUKASA OHNISHI FUMIKO INOUE TOMOKO KANOME TSUYOKI KADOFUKU NAGAHIRO SAIJO MITSURU ADACHII TOHRU OHMORI |
| description | Tumor cells that have acquired resistance to gefitinib may complicate the future treatment of patients with non-small cell
lung cancer (NSCLC). To investigate the mechanisms of acquired resistance, an acquired gefitinib-resistant cell line, PC-9/ZD2001,
has been established using a gefitinib-sensitive NSCLC cell line, PC-9. PC-9/ZD2001 showed collateral sensitivity to tumor
necrosis factor (TNF)-α. Bortezomib is a proteasome inhibitor and enhances TNF-α-induced cell death. These observations suggest
that the combination of bortezomib and TNF-α might have effects against gefitinib-resistant cells. To verify this hypothesis,
a combination effect between these drugs was examined using MTT assay and immunoblotting. This combination showed synergistic
cytotoxic effect in NSCLC cell lines with either acquired or intrinsic gefitinib resistance. However, this combination effect
was not observed in gefitinib-sensitive cells. On the other hand, bortezomib inhibited TNF-α-induced IκB degradation in all
cell lines. From these observations, it is concluded that the combination of bortezomib and TNF-α could be used to overcome
gefitinib-resistance. |
| format | Article |
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lung cancer (NSCLC). To investigate the mechanisms of acquired resistance, an acquired gefitinib-resistant cell line, PC-9/ZD2001,
has been established using a gefitinib-sensitive NSCLC cell line, PC-9. PC-9/ZD2001 showed collateral sensitivity to tumor
necrosis factor (TNF)-α. Bortezomib is a proteasome inhibitor and enhances TNF-α-induced cell death. These observations suggest
that the combination of bortezomib and TNF-α might have effects against gefitinib-resistant cells. To verify this hypothesis,
a combination effect between these drugs was examined using MTT assay and immunoblotting. This combination showed synergistic
cytotoxic effect in NSCLC cell lines with either acquired or intrinsic gefitinib resistance. However, this combination effect
was not observed in gefitinib-sensitive cells. On the other hand, bortezomib inhibited TNF-α-induced IκB degradation in all
cell lines. From these observations, it is concluded that the combination of bortezomib and TNF-α could be used to overcome
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lung cancer (NSCLC). To investigate the mechanisms of acquired resistance, an acquired gefitinib-resistant cell line, PC-9/ZD2001,
has been established using a gefitinib-sensitive NSCLC cell line, PC-9. PC-9/ZD2001 showed collateral sensitivity to tumor
necrosis factor (TNF)-α. Bortezomib is a proteasome inhibitor and enhances TNF-α-induced cell death. These observations suggest
that the combination of bortezomib and TNF-α might have effects against gefitinib-resistant cells. To verify this hypothesis,
a combination effect between these drugs was examined using MTT assay and immunoblotting. This combination showed synergistic
cytotoxic effect in NSCLC cell lines with either acquired or intrinsic gefitinib resistance. However, this combination effect
was not observed in gefitinib-sensitive cells. On the other hand, bortezomib inhibited TNF-α-induced IκB degradation in all
cell lines. From these observations, it is concluded that the combination of bortezomib and TNF-α could be used to overcome
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lung cancer (NSCLC). To investigate the mechanisms of acquired resistance, an acquired gefitinib-resistant cell line, PC-9/ZD2001,
has been established using a gefitinib-sensitive NSCLC cell line, PC-9. PC-9/ZD2001 showed collateral sensitivity to tumor
necrosis factor (TNF)-α. Bortezomib is a proteasome inhibitor and enhances TNF-α-induced cell death. These observations suggest
that the combination of bortezomib and TNF-α might have effects against gefitinib-resistant cells. To verify this hypothesis,
a combination effect between these drugs was examined using MTT assay and immunoblotting. This combination showed synergistic
cytotoxic effect in NSCLC cell lines with either acquired or intrinsic gefitinib resistance. However, this combination effect
was not observed in gefitinib-sensitive cells. On the other hand, bortezomib inhibited TNF-α-induced IκB degradation in all
cell lines. From these observations, it is concluded that the combination of bortezomib and TNF-α could be used to overcome
gefitinib-resistance.</abstract><pub>International Institute of Anticancer Research</pub><pmid>19528497</pmid></addata></record> |
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| title | Combination Effect between Bortezomib and Tumor Necrosis Factor α on Gefitinib-resistant Non-small Cell Lung Cancer Cell Lines |
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