Studies on the inhibitory effect of uremic toxins on proliferation of cultured tumor cells Comparison between serum and urine from normal subjects and uremic patients

It is well known that uremic toxins have inhibitory effects on several normal cell functions, but little is known about their role in highly proliferative cells such as tumor cells. Therefore this study using hexosaminidase assay was undertaken to determine whether uremic toxins have inhibitory effects on tumor cell proliferation. In cultured HCC cells, samples containing 30% uremic serum inhibited cell proliferation completely, while after hemodialysis, those containing the same concentration of serum showed 50% inhibition. On the other hand, samples containing 3% 10-fold concentrated urine obtained from a chronic renal failure patient did not affect the cell proliferation at all, but samples containing only 1% 10-fold concentrated urine obtained from a normal subject showed 50% inhibition. Two other cell lines, P3U1 and NUGC-4, gave almost the same results. The 2nd peak fractionated from 10-fold concentrated normal urine by Sephadex G-15 column chromatography inhibited the cell proliferation most strongly. These data suggest that uremic toxins directly inhibit the proliferation of tumor cells, which might be subsequently modified in uremic patients with malignant tumors.