Growth Inhibitory Effects of Antifolates Against an Adriamycin-Resistant Human Small Cell Lung Cancer Cell Line

Keisuke Matsuo, Katsuyuki Kiura, Hiroshi Ueoka, Masahiro Tabata, Takuo Shibayama, Tadashi Matsumura, Nagio Takigawa, Shunkichi Hiraki, Mine Harada

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3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)121-127
Number of pages7
JournalActa medica Okayama
Volume51
Issue number3
Publication statusPublished - Jun 1 1997

Keywords

  • Adriamycin-resistant cell line
  • Antifolates
  • Small cell lung cancer

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Matsuo, K., Kiura, K., Ueoka, H., Tabata, M., Shibayama, T., Matsumura, T., Takigawa, N., Hiraki, S., & Harada, M. (1997). Growth Inhibitory Effects of Antifolates Against an Adriamycin-Resistant Human Small Cell Lung Cancer Cell Line. Acta medica Okayama, 51(3), 121-127.