Abstract
Irinotecan is one of the most active drugs used in the treatment of small cell lung cancer (SCLC). 7-Ethyl-10-hydroxy-camptothecin (SN-38) is an active metabolite of irinotecan. We established an SN-38-resistant subline (SBC-3/SN-38) by continuous exposure of SN-38 to a human SCLC cell line, SBC-3. Using the 3-[4, 5-dimethyl-thiazol-2-yl] 2, 5-diphenyltetrazolium bromide assay, we evaluated the cytotoxicity of 17 anticancer agents. The SBC-3/SN-38 cells were 73-fold more resistant than the parental SBC-3 cells to SN-38 and showed cross-resistance not only to topoisomerase (topo) I inhibitors (irinotecan and topotecan), but also to topo II inhibitors (adriamycin and etoposide), antimicrotubule agents (vincristine, vindesine, vinorelbine and docetaxel), alkylating agents (cyclophosphamide and ifosfamide), platinum (cisplatin and carboplatin) and antifolate (methotrexate). Interestingly, the resistant subline reserved the sensitivity to bleomycin and 5-fluorouracil. The SBC-3/SN-38 cells had decreased topo I and II activity compared to the parent cells. The SN-38-resistant cell line, SBC-3/SN-38, will be useful to elucidate the mechanism of action of the topo I inhibitors.
| Original language | English |
|---|---|
| Pages (from-to) | 3911-3916 |
| Number of pages | 6 |
| Journal | Anticancer Research |
| Volume | 24 |
| Issue number | 6 |
| Publication status | Published - Nov 2004 |
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Keywords
- Drug resistance
- Irinotecan
- Small cell lung cancer
- Topoisomerase
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Establishment of a 7-ethyl-10-hydroxy-camptothecin-resistant small cell lung cancer cell line. / Chikamori, Masakazu; Takigawa, Nagio; Kiura, Katsuyuki; Tabata, Masahiro; Shibayama, Takuo; Segawa, Yoshihiko; Ueoka, Hiroshi; Ohnoshi, Taisuke; Tanimoto, Mitsune.
In: Anticancer Research, Vol. 24, No. 6, 11.2004, p. 3911-3916.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Establishment of a 7-ethyl-10-hydroxy-camptothecin-resistant small cell lung cancer cell line
AU - Chikamori, Masakazu
AU - Takigawa, Nagio
AU - Kiura, Katsuyuki
AU - Tabata, Masahiro
AU - Shibayama, Takuo
AU - Segawa, Yoshihiko
AU - Ueoka, Hiroshi
AU - Ohnoshi, Taisuke
AU - Tanimoto, Mitsune
PY - 2004/11
Y1 - 2004/11
N2 - Irinotecan is one of the most active drugs used in the treatment of small cell lung cancer (SCLC). 7-Ethyl-10-hydroxy-camptothecin (SN-38) is an active metabolite of irinotecan. We established an SN-38-resistant subline (SBC-3/SN-38) by continuous exposure of SN-38 to a human SCLC cell line, SBC-3. Using the 3-[4, 5-dimethyl-thiazol-2-yl] 2, 5-diphenyltetrazolium bromide assay, we evaluated the cytotoxicity of 17 anticancer agents. The SBC-3/SN-38 cells were 73-fold more resistant than the parental SBC-3 cells to SN-38 and showed cross-resistance not only to topoisomerase (topo) I inhibitors (irinotecan and topotecan), but also to topo II inhibitors (adriamycin and etoposide), antimicrotubule agents (vincristine, vindesine, vinorelbine and docetaxel), alkylating agents (cyclophosphamide and ifosfamide), platinum (cisplatin and carboplatin) and antifolate (methotrexate). Interestingly, the resistant subline reserved the sensitivity to bleomycin and 5-fluorouracil. The SBC-3/SN-38 cells had decreased topo I and II activity compared to the parent cells. The SN-38-resistant cell line, SBC-3/SN-38, will be useful to elucidate the mechanism of action of the topo I inhibitors.
AB - Irinotecan is one of the most active drugs used in the treatment of small cell lung cancer (SCLC). 7-Ethyl-10-hydroxy-camptothecin (SN-38) is an active metabolite of irinotecan. We established an SN-38-resistant subline (SBC-3/SN-38) by continuous exposure of SN-38 to a human SCLC cell line, SBC-3. Using the 3-[4, 5-dimethyl-thiazol-2-yl] 2, 5-diphenyltetrazolium bromide assay, we evaluated the cytotoxicity of 17 anticancer agents. The SBC-3/SN-38 cells were 73-fold more resistant than the parental SBC-3 cells to SN-38 and showed cross-resistance not only to topoisomerase (topo) I inhibitors (irinotecan and topotecan), but also to topo II inhibitors (adriamycin and etoposide), antimicrotubule agents (vincristine, vindesine, vinorelbine and docetaxel), alkylating agents (cyclophosphamide and ifosfamide), platinum (cisplatin and carboplatin) and antifolate (methotrexate). Interestingly, the resistant subline reserved the sensitivity to bleomycin and 5-fluorouracil. The SBC-3/SN-38 cells had decreased topo I and II activity compared to the parent cells. The SN-38-resistant cell line, SBC-3/SN-38, will be useful to elucidate the mechanism of action of the topo I inhibitors.
KW - Drug resistance
KW - Irinotecan
KW - Small cell lung cancer
KW - Topoisomerase
UR - http://www.scopus.com/inward/record.url?scp=14944382966&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=14944382966&partnerID=8YFLogxK
M3 - Article
C2 - 15736431
AN - SCOPUS:14944382966
VL - 24
SP - 3911
EP - 3916
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 6
ER -