一种Palbocilib衍生物抗肝癌活性研究

Study on Anticancer Activity of Palbocilib Derivative on Hepatocellular Carcinoma

目的 研究Palbocilib衍生物PB的抗肝癌活性。方法 取对数生长期的细胞分为阴性对照组、Palbocilib组和Palbocilib衍生物(PB)处理组,药物作用细胞72 h后用SRB法测定对MCF-7细胞和HepG2细胞增殖抑制作用;建立人HepG2裸鼠皮下移植瘤模型,连续灌胃给药21 d,每3天测瘤体积和称重一次,试验结束解剖称取肿瘤和主要脏器重量,计算相对肿瘤增殖率T/C%、抑瘤率和脏器系数。结果 PB对HepG2和MCF-7细胞增殖抑制作用的IC50分别是32.26μmol/L和139.50μmol/L;Palbocilib对HepG2和MCF-7细胞增殖抑制作用的IC50分别是129.69μmol/L和17.69μmol/L,PB对HepG2的抑制作用好于Palbocilib。PB对HepG2裸鼠移植瘤的相对肿瘤增殖率(T/C%)为58.06%;抑瘤率为40.76%;体重未出现明显降低,脏器重量、脏体系数和脏脑系数除了心脏显著低于模型对照组外,肝脏、脾脏、肺脏、脑、卵巢和子宫的重量和脏器系数与模型组无统计学差异。结论 PB能抑制HepG2肝癌肿瘤细胞的增殖和HepG2肝癌裸鼠移植瘤的生长,是一种抗肝癌的潜在靶向药物;在连续给药剂量条件下未出现体重降低,无明显的脏器毒性。

Objective To investigate the anticancer activity of Palbocilib derivative(PB)on hepatocellular carcinoma.Methods MCF-7 cells and HepG2 cells were treated with PB or palbocilib for 72 h,and then the anti-proliferative activity was determined by SRB method.The human HCC xenografts in vivo were established with nude mice and HepG2 cells.PB was administered by gavage for 21 consecutive days.The body weight and tumor volume were measured each 3 days during administration.The weight growth rate,tumor inhibiting rate and organ coefficient were measured.Results The IC50 for HepG2 and MCF-7 cells of PB were 32.26μmol/L and 139.50μmol/L,while the IC50 of Palbocilib were 129.69μmol/L and 17.69μmol/L,which showed PB had a better inhibitory effect on HepG2 than Palbocilib.The relative tumor proliferation rate(T/C%)of PB on HepG2 nude mouse transplanted tumors was 58.06%.The tumor inhibition rate was 40.76%.There was no significant decrease in body weight.The organ weight and organ coefficient of the heart were significantly lower than the model control group(P<0.05).The weight and organ coefficients of the liver,spleen,lungs,brain,ovaries and uterus were not statistically different from the model group.Conclusion PB is a potential targeted drug against liver cancer,which can significantly inhibit HepG2 cells proliferation and xenografts growth.Under continuous dosing conditions,there is no weight loss or significant organ toxicity.