水溶性紫杉醇衍生物PLT抗肿瘤活性的实验研究

Preliminary Study on Antitumor Activity of Taxol Derivative

目的:观察水溶性紫杉醇衍生物(Peg-Leu-Taxol,PLT)的抗肿瘤活性及机制。方法:以MTT还原法检测PLT对肿瘤细胞生长的抑制作用,以相差显微镜和荧光显微镜观察细胞形态学改变,免疫组化方法检测细胞生长相关基因p21^(wafl)表达。结果:PLT能明显抑制乳腺癌(MCF-7)、非小细胞肺癌(PG-49)和红白血病(K562)细胞的生长。细胞形态呈凋亡特征性改变,细胞皱缩,核染色质凝缩、碎裂、亮珠状浓染。细胞p21砌蛋白表达显著增高。结论:PLT具有明显的抗肿瘤活性,其诱导肿瘤细胞凋亡与p21^(wafl)基因表达上调有关。

To study the effect of taxol derivative (Peg-Leu-Taxol, PLT) on human cancer. Methods: The growth in-hibiton of human breast cancer cell line (MCF-7), non-small cell lung cancer cell line (PG-49), and leukemia cell line (K562) were analyzed by MTT assay. Morphological changes of cell were performed with phase contrast microscopy and transmission electron microscopy. The level of p21wafl protein was measured with immunocytochemisty. Results: After 48 hours of exposure to PLT, the growth of MCF-7, PG-49, and K562 cells were remarkably inhibited. The apoptosis of MCF-7 cells presented some morphologic features of apoptosis, including cell shrinkage, nuclear condensation, and formation of apoptotic body. Moreover, PLT increased the p21wafl gene expression in MCF-7 cells. Conclusion: Our results indicate that PLT can inhibit the growth of cancer cells by affecting the gene expression related to cell cycle progression.