Modulation of cisplatin sensitivity and resistance by buthionine sulfoximine and cyclosporin A in human esophageal cancer cells

Abstract

We established a 2.4-fold cisplatin (CDDP)-resistant human esophageal cancer cell line (TE2R) from the parent TE2 line. CDDP accumulation was reduced in TE2R. The Na+, K+-ATPase inhibitor ouabain inhibited CDDP accumulation in TE2 but not TE2R, suggesting that TE2R may have alterations in the Na+, K+-ATPase and defective CDDP uptake mechanism. Buthionine sulfoximine (BSO) enhanced CDDP sensitivity of both cell lines and cyclosporin A (CsA) modified CDDP resistance in TE2R. These effects were associated with increased CDDP accumulation. Thus, BSO and CsA may be useful for modulation of CDDP sensitivity or resistance in esophageal cancer.