多肽HM-3对人非小细胞肺癌裸鼠移植瘤抑制作用研究

Antitumor effects of peptide HM-3 against non-small cell lung cancer xenografts in nude mice

目的检测HM-3类不同血管生成抑制剂治疗人非小细胞肺癌裸鼠移植瘤的药效学,考察血管生成抑制剂与肿瘤微环境的相互作用,为临床确定治疗方案提供参考和依据。方法建立人非小细胞肺癌A549的裸鼠移植瘤模型,以多西他赛(10 mg·kg^(-1))为阳性对照药物,评价了在肿瘤体积≥300 mm^3给予有效、过高剂量HM-3和贝伐单抗对肿瘤生长的抑制作用。结果动物实验表明,肿瘤的体积≥300mm^3给药,阳性对照组多西他赛具有很好的抗肿瘤活性。G2多西他赛(10 mg·kg^(-1))组的瘤重抑瘤率为60.80%。G3 HM-3(3 mg·kg^(-1))组、G4 HM-3(48 mg·kg^(-1))组、G5Avastin(5 mg·kg^(-1))组抑瘤效果不佳,瘤重抑瘤率分别为43.60%、-34.80%、44.40%。结论由于受肿瘤生长阶段、肿瘤微环境、作用靶点等影响,血管生成抑制剂HM-3有一定抑制肿瘤生长的效果,但效果不佳。HM-3抑瘤效果在(0~6 mg·kg^(-1))范围内存在剂量依赖关系。而HM-3(48mg·kg^(-1))过高剂量对人非小细胞肺癌A549裸鼠移植瘤无抑制作用,表现促进作用。特殊量效关系提示临床使用血管抑制剂时应注意使用剂量。

Aims To evaluate the pharmacodynamic efficacy of different types of antiangiogenic agents as HM-3 on a non-small cell lung cancer xenografts tumor model. To explore the interaction between the antiangiogenic agents and the tumor microenvironment,and to offer suggestions for clinical therapy. Methods The non-small cell lung carcinoma xenograft model was established in Balb / c nude mice. The model mice were treated with Docetaxel( 10 mg ·kg^(-1)) as the positive control. The mice were parallelly treated with,HM-3 at the doses of 3 mg · kg^(-1)and 48 mg · kg^(-1)and,Avastin( 5 mg·kg^(-1)). The parameters include tumor volume,tumor weight and immunohistochemical analysis. Result Animal experiments showed that docetaxel had good anti-tumor activity. Tumor growth inhibition by tumor weight of G2 docetaxel( 10 mg·kg^(-1)) group was 60. 80%. Tumor growth inhibition by tumor weight of G3 HM-3( 3 mg·kg^(-1)) group,G4 HM-3( 48 mg·kg^(-1)) group,G4 Avastin( 5 mg·kg^(-1)) group,were43. 60%,- 34. 80%,44. 40%,respectively. Conclusion The antigiogenic effect is affected by tumor growth stage,tumor microenvironment and their working mechanisms. Angiogenesis inhibitors HM-3 has a certain effect of inhibiting tumor growth,but to little avail. HM-3 shows on inhibitory effect in a dose-dependent manner at the doses of 0 ~ 6 mg·kg^(-1). HM-3at a high dose of 48 mg · kg^(-1)has no inhibitory but promoting effects on human non-small cell lung carcinoma A549 xenografts in nude mice. Special doseeffect relationship indicates that dosage should be paid attention to in the clinical use of blood vessel inhibitors.