Appearance of drug-resistant tumor cells in a maxillary cancer patient undergoing chemotherapy and chemoradiotherapy

Abstract

In this study, we examine drug resistance and sensitivity in tumor cell lines cultured from a patient undergoing prolonged chemotherapy. Four serially established primary tumor cell lines (KKM-A, -B, -C, and -D) were cultured from a case of maxillary sinus carcinoma: KKM-A from the nontreated primary tumor; KKM-B from the residual tumor after chemotherapy with cisplatin (CDDP) and 5-fluorouracil (5-FU); KKM-C from the local tumor that recurred following complete remission with chemoradiotherapy (combination of 5-FU, vitamin A, and radiation); and KKM-D from a metastatic lymph node tumor after further chemotherapy with CDDP and peplomycin. The sensitivity of the four cell lines to CDDP, 5-FU, bleomycin (BLM), carboquone (CQ), and colchicine was assessed according to the reduction in colony formation. The KKM-A cell line was very sensitive to CDDP, BLM, CQ, and colchicine, whereas the posttreatment cell lines were resistant to these four drugs. The resistant cell lines were probably selected as a result of chemotherapy and radiotherapy. The nontreated KKM-A cell line was naturally somewhat resistant to 5-FU. The 5-FU-resistance of the KKM-B, -C, and -D cell lines was reduced in that order, corresponding to their relative degree of treatment. The KKM-D cell line from the metastatic lymph node showed a different sensitivity from the KKM-B and -C cell lines from the primary site, suggesting a heterogeneity in drug sensitivity between primary and metastatic tumor cells.