Evaluation of Paclitaxel as a Non-Cross-Resistant Agent in Cisplatin-Resistant Small Cell Lung Cancer (SCLC)

Abstract

Small Cell Lung Cancer (SCLC) is an aggressive disease with early metastasis and poor prognosis. Etoposide and cisplatin/carboplatin are used in the first-line treatment of SCLC. Amrubicin is the only established second-line treatment for SCLC only in Japan but not in western world. Therefore, there is a severe need for active agents for second-line treatment of therapy-resistant SCLC. Currently, paclitaxel has shown a degree of cytotoxic activity against SCLC only in phase II studies. This research aims to establish human SCLC cell lines resistant to cisplatin and evaluate the efficacy of paclitaxel on established cisplatin-resistant cell lines. I cultured human SCLC cell lines N417 and H82 and treated with different concentrations of cisplatin and performed WST-8 assay for comparing effectiveness of cisplatin and paclitaxel. Parental N417 cells were serially passaged (>50 times) to establish the cisplatin-resistant subline N417/CDDP; however, H82 cells were highly sensitive towards cisplatin. Although we did not obtain H82-derived resistant cell line, parental H82 cells started to show sensitivity from 0.3 μM and we evaluate cell viability with 0.5 μM cisplatin-treated H82 cells for comparing. We found cisplatin decrease the cell viability only for parental N417 and H82 cell lines but not for N417/CDDP and 0.5 μM cisplatin-treated H82 cell line, but paclitaxel showed a stronger response not only in parental cell lines but also in cisplatin-resistant and cisplatin-treated cell lines.