大鼠肝癌细胞与间充质干细胞药敏相关性研究

Correlation of Antitumor Drug Sensitivity between Marrow Mesenchymal Stem Cells (MSCs)and Hepatocarcinoma Cells in Rats

背景与目的:探索针对肿瘤干细胞的药物敏感实验,对提高肝癌等实体瘤化疗有效率意义重大。在肝癌中,来自于骨髓干细胞的卵圆细胞是对应的成体干细胞。鉴于目前肿瘤干细胞和卵圆细胞分离困难,我们研究肝癌大鼠间充质干细胞与肿瘤细胞药敏相关性,探讨利用间充质干细胞代替肝癌肿瘤干细胞进行药物敏感实验的可能性。方法:以二乙基亚硝胺为诱癌剂制造大鼠肝癌模型。分离培养间充质干细胞与肝癌细胞,MTT法检测阿霉素(0.2μg/ml)、氟尿嘧啶(5μg/ml)及顺铂(1μg/ml)作用24h对细胞抑制率。化疗药物作用后的肝癌细胞移植裸鼠,6周后测量移植瘤重量。阿霉素、氟尿嘧啶及顺铂对这两种细胞抑制率以及对应药物作用后肝癌细胞移植瘤重量间进行相关性分析。结果:①3种药物对肝癌细胞抑制率与其作用肝癌细胞后移植瘤重量间进行相关性分析,具体偏相关系数为:阿霉素,0.6307(P>0.05);氟尿嘧啶,0.4358(P>0.05);顺铂,0.7080(P>0.05);②3种常用肝癌化疗药物对肝癌大鼠间充质干细胞抑制率与对肝癌细胞间抑制率进行相关性分析,具体偏相关系数为:阿霉素,0.6316(P>0.05);氟尿嘧啶,0.4214(P>0.05);顺铂,0.5943(P>0.05);药物对大鼠间充质干细胞抑制率与对应药物作用后肝癌细胞移植瘤重量有较好负相关性,具体偏相关系数为:阿霉素,-0.8308(P<0.05);氟尿嘧啶,-0.8991(P<0.01);顺铂,-0.8311(P<0.05)。结论:化疗药物对肝癌细胞抑制率与对应药物作用后肝癌细胞移植瘤重量无相关性,常规药物敏感实验不能完全反映肝癌增殖侵袭能力。化疗药物对间充质干细胞抑制率与对应药物作用后肝癌细胞移植瘤重量有负相关,可以较好地反映肝癌细胞增殖侵袭能力。

BACKGROUND ＆ OBJECTIVE： As hepatocarcinoma stem cells may originate from oval cells and oval cells are difficult to be separated and purifid, MSCs （marrow mesenchymal stem cells）, which are the progenitor cells of the hepatocarcinoma stem cells, were selected instead in our stuy to investigate the correlation of anticancer drug sensitivity between hepatocarcinoma cells and MSCs in rats. METHODS： The primary liver carcinoma modle of rats was induced by diethylnitrosamine. Tumor cells and MSCs from eight hepatocarcinoma rats were separated. The inhibitory effects of 3 anticancer drugs [adriacin （0.04 μg/ml）,cisplatin （0.2 μg/ml） and fluorouracil（1 μg/ml）] to hepatocarcinoma cells and MSCs were measured by MTT assay. The weight of the tumor in nude mice which were injected with rat hepatocarcinoma cells was measured after 6 weeks. Then the correlation of the inhibitory ratio of 3 anticancer drugs to hepatocarcinoma cells and MSCs, and to the tumor weight of nude mice was analyzed. RESULTS： No correlation was revealed between the inhibitory ratio of 3 anticancer drugs to hepatocarcinoma cells and the tumor weights of nude mice injectal with drug treated tumor cells. The correlation coefficient was：0.6307 （adriacin, P〉0.05）, 0.4358 （fuiorouracil, P〉0.05） and 0.7080 （cisplatin, P〉0.05）. No correlation was observed between the inhibitory ratio of 3 anticancer drugs to hepatocarcinoma cells and to MSCs. The correlation coefficient was： 0.6316 （adriacin, P〉0.05）, 0.4214（fluorouracil, P〉0.05） and 0.5943（cisplatin, P〉 0.05）. However, significant reverse correlation was found between the inhibitory ratio of 3 anticancer drugs to MSCs and the tumor weights of nude mice injectal with drug treated tumor cells. The correlation coefficient was： -0.8308 （adriacin, P〈0.05）, -0.8991 （fluorouracil, P〈0.01） and -0.8311 （cisplatin, P〈0.05）. CONCLUSIONS： Conventional anticancer drug sensitivity experiments could not reflect the chemoresistance of the hepatocarcinoma cells. However the inhibitory ratio of the anticancer drugs to MSCs in the hepatocarcinoma rats can reflect the chemoresistance of hepatocarcinoma cells accordingly.