Antiproliferative effect of interferon-alpha on human renal cell carcinoma in clonogenic assay--single and combination effect with cancer chemotherapeutic agent
Ohmura, K.; Tsukamoto, T.
Hinyokika Kiyo. Acta Urologica Japonica 35(5): 737-747
1989
ISSN/ISBN: 0018-1994 PMID: 2801371 Document Number: 346633
With human tumor clonogenic assay, the direct antiproliferative activity of recombinant human leukocyte interferon alpha (IFN-alpha) was investigated on human renal cell carcinomas (RCCs), which consisted of a human RCC cell line (ACHN), two human RCC xenografts and fifteen primary RCCs. The combination effect of IFN-alpha with a cancer chemotherapeutic agent was studied, as well, with the assay system. IFN-alpha showed a dose-dependent antiproliferative activity against the human RCCs. The clonal growth of ACHN cell line was inhibited by less than 50% at the concentration of 1,000 IU/ml. Two xenografts had a different sensitivity to IFN-alpha, in which the percent colony formation was less than 20% in RCC-3 at the concentration of 100-100,000 IU/ml, while in RCC-4 more than 50% even at the high concentration of 10,000 IU/ml. In 15 primary tumors obtained at surgery, two types of response to IFN-alpha were demonstrated. One was the response in which the colony formation was inhibited in a dose-dependent manner as an increment of IFN-alpha concentration, and the other in which the colony formation was not sufficiently inhibited even at the high concentration of IFN-alpha. The dose-dependent inhibition of colony formation was demonstrated in 10 out of 15 specimens (66.7%). When the colony formation suppressed to less than 50% of control was considered to be sensitive to IFN-alpha, 6.7% of these 15 primary tumors were sensitive to IFN-alpha at 100 IU/ml, 20.0% at 1,000 IU/ml and 20.0% at 10,000 IU/ml. Combination effects of IFN-alpha and with each of four different cancer chemotherapeutic agents (vinblastine, adriamycin, methotrexate, 5-fluorouracil) were investigated on the ACHN cell line. Every combination type produced a subadditive or synergistic combination effect. In particular, the combination of IFN-alpha with vinblastine of more than 0.1 microgram/ml concentration yielded a combination effect of statistical significance (p less than 0.001). Even against premary tumors, the combination of IFN-alpha with vinblastine showed a synergistic effect in one out of every three tumors. These results suggested that the combination of IFN-alpha with a cancer chemotherapeutic agent would enhance the clinical effect of IFN-alpha alone in only a certain situation.