PURPOSE: KRN5500 is a new derivative of spicamycin produced by Streptomyces alanosinicus and is known to have a wide range of antitumor activities against human cancer cell lines. Because of its unique structure, this compound seems to have a different mode of action from other antitumor drugs and nonoverlapping toxicities. Therefore, KRN5500 is expected to be a suitable candidate for combination chemotherapy. METHODS: We investigated the effects of combinations of KRN5500 and other anticancer drugs on the growth of a human non-small-cell lung cancer cell line, PC14, using a revised three-dimensional model. RESULTS: Synergism was observed when KRN5500 and cisplatin were combined at concentrations in the ranges 0.005 to 0.25 microg/ml and 0.025 to 0.25 microg/ml, respectively. In combination with carboplatin, an analog of cisplatin, and etoposide, a marked synergistic interaction was also found. CONCLUSION: These results suggest the usefulness of combinations of KRN5500 with cisplatin, carboplatin or etoposide for chemotherapy for non-small-cell lung cancer.
PURPOSE:KRN5500 is a new derivative of spicamycin produced by Streptomyces alanosinicus and is known to have a wide range of antitumor activities against humancancer cell lines. Because of its unique structure, this compound seems to have a different mode of action from other antitumor drugs and nonoverlapping toxicities. Therefore, KRN5500 is expected to be a suitable candidate for combination chemotherapy. METHODS: We investigated the effects of combinations of KRN5500 and other anticancer drugs on the growth of a human non-small-cell lung cancer cell line, PC14, using a revised three-dimensional model. RESULTS: Synergism was observed when KRN5500 and cisplatin were combined at concentrations in the ranges 0.005 to 0.25 microg/ml and 0.025 to 0.25 microg/ml, respectively. In combination with carboplatin, an analog of cisplatin, and etoposide, a marked synergistic interaction was also found. CONCLUSION: These results suggest the usefulness of combinations of KRN5500 with cisplatin, carboplatin or etoposide for chemotherapy for non-small-cell lung cancer.