A study on direct antitumor activity of bropirimine (oral interferon inducer) for renal cell carcinoma

Abstract

腎細胞癌17例の腎摘時採取した腫瘍を用いた器官培養法, ならびにヌードマウス移植継代可能株となった1株を用いて, bropirimineの直接的抗腫瘍効果を検討した。器官培養法では, 17例中15例が対照群に比べて3H-thymidine uptakeが有意に抑制された。ヌードマウス可移植性(Epo産生株)となった1株(JRC 901)に対するbropirimineの経口投与では, bropirimineの濃度依存性に腫瘍増殖が抑制されたが, 対照群間に有意差はなく, かつ組織学的にもviableな腫瘍細胞の完全消失はえられなかった。しかし, JRC 901株のEpo産生量は対照群に比べて有意に抑制された

Aryl pyrimidinones, including bropirimine, exert anti-tumor activity through the induction of interferon (IFN)-alpha. Herein, the direct anti-tumor effect of bropirimine on 17 renal cell carcinoma (RCC) surgically obtained was examined using an organ culture system closely resembling the in vivo state, and also using the heterotransplanted nude mouse system. The findings obtained using the organ culture system showed that bropirimine inhibited 3H-thymidine uptake significantly in 15 of the 17 RCC (88.2%) compared with the control. Furthermore, the 3H-thymidine uptake was dose-dependently inhibited in 3 of the 17 tumors (17.6%). The oral administration of bropirimine against RCC heterotransplanted in nude mice (JRC 901: an erythropoietin-producing strain) tended to inhibit tumor growth dose-dependently, but not significantly (mean tumor weight ratio: T/C ratio: over 43%, degeneration degree of tumor: incomplete). However, the production of erythropoietin from the JRC 901 was significantly inhibited. These findings suggest that bropirimine has a direct anti-tumor activity, without the mediation of IFN-alpha induction, against human renal cell carcinoma.