Inhibitory effects of suramin on a human renal cell carcinoma line, causing nephrogenic hepatic dysfunction.
A sarcomatoid renal cell carcinoma has been isolated from a patient with Stauffer's syndrome. The tumor, designated BA1119, has been established in tissue culture over 80 passages. Subcutaneous deposition of BA1119 in athymic mice induced splenomegaly and hepatic dysfunction which became fatal within four weeks without metastasis. Suramin is a synthetic polyanionic compound which is capable of altering the function of a number of biologic systems and inhibiting the activity of a variety of protein and growth factors. In this study we attempted to study the effect of suramin on growth of BA1119 in culture and in nude mice. Suramin, at 300 micrograms/ml., had a profound inhibitory effect on cell growth during a six-day culture period. Suramin given i.p. weekly to nude mice at clinically relevant doses (200 mg./kg.) caused significant shrinkage of subcapsular tumor deposits. Splenic hypertrophy secondary to BA1119-induced Stauffer's syndrome was inhibited by suramin. Synergistic effect with enhanced cytotoxicity on BA1119 cells was observed when suramin (100 micrograms/ml.) was used in combination with lymphokines, such as gamma interferon (500 units/ml.) and alpha tumor necrosis factor (300 ng./ml.). These results may suggest a therapeutic efficacy of suramin in renal cell carcinoma patients with Stauffer's syndrome.
Chang
S Y
SY
Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Yu
D S
DS
Sherwood
E R
ER
Kozlowski
J M
JM
Lee
C
C
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D002455:Cell Division / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D013498:Suramin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000627:therapeutic use
D014409:Tumor Necrosis Factor-alpha; D013498:Suramin; D007371:Interferon-gamma