키토산 유도체인 Sulfated N-acetyl Chitosan의 종양전이 억제효과

Inhibitory Effects of Tumor Metastasis by Chitosan Derivative, of Sulfated N-acetyl Chitosan

키토산 유도체 인 sulfated N→acetyl chitosan을 합성하여 이 화합물을 쥐에 이식한 B16/BL6 mela noma에 대하여 폐암전이의 억제효과를 조사하였다. 키토산의 황산유도체는 13C-n.m.r.에 의하여 확인한 결과 3, 6, O-disulfate 엄을 알 수 있었다. SuI fated N-acetyl chitosan을 100mg/kg을 투여하였을 때 B16/BL6의 melanoma cells을 가장 효과적 으로 억제하였고 종양 무게의 증식도 대조군에 비해 억제되었다. 폐암의 전이에 있어서 B16/BL6에 sulfated N-acetyl chitosan을 LV. V로 주사하였을 때 B16/BL6의 melanoma의 전이 세포의 수는 자발적인 전이에 있어서도 용량 의존형(20 ~ 1OOmg/kg) 에 따라 줄어들었다. B16/BL6을 접종한 후 sulfated N-acetyl chitosan을 I.V.로 투여했을 때 전이세 포의 수는 현저히 감소하였다. Sulfated N-acetyl chitosan은 laminin의 종양세포에의 세포접착 능력을 부분적으로 억제하였다. 이와 같은 결과는 chitosan의 유도체인 sulfated N-acetyl chitosan이 세포접착 능력이 실험적으로 자발적인 암전이 모델에 효과적으로 작용하였다.

Chitosan derivative, of a sulfated N-acetyl chitosan was synthesized, and the inhibitory effects of this compound on the experimental and spontaneous lung metastallc B16/BL6 melanoma bearing mice were investigated. Position of substitution with sulfate in water-soluble sulfated derivatives of chitosan were analysed by 13C-nmr. The structure of N-acetyl chitosan 3,6 0-disulfate were confirmed. The tumor growth inhibition of B16/BL6 melanoma cells has been shown at the highest level of 77.6% when sulfated N-acetyl chitosan were administered at the dose of 100mg/kg. In the lung metastasls, the sulfated N-atetyl chitosan was administered to C57BL/6B mice bearing B16/BL6 melanoma cells by I.V. injection and the number of metastasis foci of melanoma were decreased by the dose dependent manner ranging from 20 to 100mg/kg. In the spontaneous metastasis, I.V. administrations of sulfated N-acetyl chitosan after tumor inoculation resulted in marked reduction of metastatic colonies. A sulfated N-acetyl chitosan was able to partially inhibit the tumor cell adhesion by migration to laminin. These results suggested that chitosan derivative, a sulfated N-acetyl chitoasn was able to inhibit to the experimental and spontaneous metastasis models as well as cell adhesion ability.