肝脂素对小鼠S37肉瘤与B16黑色素瘤的抗肿瘤作用

The antitumor efficacy of Heplipin on S37 sarcoma and B16 melanoma in mice

目的 :探讨肝脂素 (Heplipin)对S37和B16两肿瘤细胞株移植瘤的生长抑制作用。方法 :小鼠S37肉瘤和B16黑色素瘤移植瘤在高、中、低剂量 (每天分别为 30 0 0、180 0、110 0mg kg)肝脂素胃饲为治疗组 ,环磷酰胺 (CTX)2 0mg(kg 天 )和生理盐水作为两对照组。比较抑瘤率、癌周边部血管数 ,总肿瘤面积中坏死区所占比例。结果 :肝脂素对S37肉瘤和B16黑色素瘤的抑瘤率分别为大剂量 :75 .1%和 47.0 %、中剂量 :6 9.7%和 32 .1%、小剂量 :6 1.7%和 13.0 % ,显示出明显的剂量效应关系 ,与生理盐水对照组相比有显著性差异。在S37肉瘤荷瘤小鼠的实验中 ,组织学观察发现 ,肝脂素用药组肿瘤周边部单位面积内血管数明显少于阴性对照组和CTX组 ;肝脂素治疗组的肿瘤坏死面积明显大于对照组。结论 :肝脂素可明显抑制小鼠S37肉瘤和B16黑色素瘤的生长 ,其抗肿瘤机制可能与抑制肿瘤新生血管的形成 。

Purpose:To investigate inhibitory effect of Heplipin on the growth of S37 and B16 implanted into Kunming and C57 mouse respectively. Methods:Heplipin was administrated through gastric inhabatin with the dose of each day such as 3 000 mg/kg (large dose group) 1800 mg/kg(medial dose group) and 1100 mg/kg different (small dose group). Cycolo phosphaincole(CTX, each day 20 mg/kg) and normal saline wasused as postive and negative control respectively. The rates in tumor inhibition, the number of blood vessels, and the rate of necrosis area was tested.Results:The growth suppression of Heplipin to S37 sarcoma and B16 melanoma was 75.1% (large dose, P <0.0001), 69.7% (intermediate dose, P <0.0001), 61.7% (small dose, P <0.01) in Heplipin treated S37 sarcoma laden mice; and 47.0% (large dose, P <0.01), 32.1% (intermediate dose), 13.0% (small dose) in Heplipin treated B16 melanoma laden mice. Histologic examination showed that the number of blood vessels in S37 sarcoma laden mice of large dose group (1.39/field, P <0.01) and intermediate dose group (2.15/field, P < 0.05) was less than in that of control groups (6.28/field and 4.70/field ). Heplipin treated groups had more extensive tumor necrosis (75.5% and 60.5%) than the negative control group (48.3%). Conclusions:Heplipin can significantly suppress the growth of the S37 sarcoma and B16 melanoma in mice. The anti tumor mechanism of Heplipin may be related to the inhibition of blood vessel formation resulting in ischemic necrosis of the tumor. [