TY - JOUR
T1 - Growth Inhibitory Effects of Antifolates Against an Adriamycin-Resistant Human Small Cell Lung Cancer Cell Line
AU - Matsuo, Keisuke
AU - Kiura, Katsuyuki
AU - Ueoka, Hiroshi
AU - Tabata, Masahiro
AU - Shibayama, Takuo
AU - Matsumura, Tadashi
AU - Takigawa, Nagio
AU - Hiraki, Shunkichi
AU - Harada, Mine
PY - 1997/6/1
Y1 - 1997/6/1
N2 - We have established an Adriamycin (ADM) -resistant small cell lung cancer (SCLC) cell line, SBC-3/ADM100, which shows multifactorial mechanisms of resistance to ADM, such as overexpression of P-glycoprotein, an enhanced detoxifying system and a decrease in topoisomerase II activity. In the present study, we confirmed that SBC-3/ADM 100 showed collateral sensitivity to methotrexate and TNP-351, a new antifolate, though this cell line showed a typical multidrug resistance (MDR) pattern. We also demonstrated a faster uptake and higher accumulation (1.3-fold) of TNP-351 in the SBC-3/ADM100 cells than those in the parent SBC-3 cells. These results explain one of the mechanisms for collateral sensitivity in the resistant cells. Furthermore, this cell line was found to have no cross-resistance to edatrexate and minimal cross-resistance to trimetrexate, 254-S (cisplatin analog), 5-fluorouracil and 4-hydroperoxyifosfamide. These drugs will have clinical importance in patients with SCLC who were previously treated with an ADM-containing regimen. Thus, antifolates, especially TNP-351 and edatrexate, can be expected to eradicate residual multidrug resistant SCLC cells selected by ADM.
AB - We have established an Adriamycin (ADM) -resistant small cell lung cancer (SCLC) cell line, SBC-3/ADM100, which shows multifactorial mechanisms of resistance to ADM, such as overexpression of P-glycoprotein, an enhanced detoxifying system and a decrease in topoisomerase II activity. In the present study, we confirmed that SBC-3/ADM 100 showed collateral sensitivity to methotrexate and TNP-351, a new antifolate, though this cell line showed a typical multidrug resistance (MDR) pattern. We also demonstrated a faster uptake and higher accumulation (1.3-fold) of TNP-351 in the SBC-3/ADM100 cells than those in the parent SBC-3 cells. These results explain one of the mechanisms for collateral sensitivity in the resistant cells. Furthermore, this cell line was found to have no cross-resistance to edatrexate and minimal cross-resistance to trimetrexate, 254-S (cisplatin analog), 5-fluorouracil and 4-hydroperoxyifosfamide. These drugs will have clinical importance in patients with SCLC who were previously treated with an ADM-containing regimen. Thus, antifolates, especially TNP-351 and edatrexate, can be expected to eradicate residual multidrug resistant SCLC cells selected by ADM.
KW - Adriamycin-resistant cell line
KW - Antifolates
KW - Small cell lung cancer
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M3 - Article
C2 - 9227790
AN - SCOPUS:0031157944
SN - 0386-300X
VL - 51
SP - 121
EP - 127
JO - Acta Medica Okayama
JF - Acta Medica Okayama
IS - 3
ER -
