知识与财富的链接
目的:确定去甲斑蝥素(norcantharidin,NCTD)对12类,72种人类癌症细胞的半数抑制浓度(half maximal inhibitory concentration,IC_(50)),并以此作为生长抑制效应的指标。方法:采用长时间细胞观察及功能分析系统(Incu CyteTM ZOOM),用不同浓度NCTD分别与癌细胞株共同孵育72 h,实时监测和观察细胞增殖情况,分析NCTD对12种人类癌症细胞的细胞毒性。此外,长时间细胞观察及功能分析系统的成像系统在每个时点进行拍照存档,展示了各细胞生长及存活的状态,并且进行实时观察。结果:NCTD对72株癌细胞系的生长抑制效应存在广泛的差异[IC_(50)2~66μmol·L-1,平均(24.63±12.97)μmol·L~(-1)]。NTCD对不同细胞生长抑制的影响差异明显,体现在不同癌种之间以及同种癌种内不同个体之间。这充分反映了NTCD临床疗效个体化的特征,并提示了未来个体化治疗的可能性。肝细胞癌、胃癌、前列腺癌、白血病、中枢神经系统癌、肾癌、胆管癌细胞的细胞系IC_(50)平均值均低于总平均值,且前列腺癌、白血病、中枢神经系统癌、肾癌、胆管癌细胞NCTD IC_(50)平均值与肝癌细胞系和胃癌细胞系IC_(50)平均值相近。结论:NTCD可能对前列腺癌、白血病、中枢神经系统癌、肾癌、胆管癌这几类癌症可产生显著疗效。
Objective: To determine the inhibitory effect of norcantharidin (NCTD) on the half maximal inhibitory concentration (IC50) of 72 cell lines of 12 major human cancers, in order to provide an index for growth inhibition effect. Method: The inhibitory effect of norcantharidin (NTCD) was determined by measuring and observing the half maximal inhibitory concentration (IC50) for individual cell lines using an IncuCyteTM ZOOM-based proliferation assay. Briefly, cells of individual lines at defined densities were treated with norcantharidin at various concentration, and their relative growth rates were assessed by measuring the relative cell densities once every 3 hours for 72 hours. In addition, digital images were captured at each time point and recorded. Result: The IC50 of NCTD for the 72 cancer cell lines varied considerably, ranging from 2 to 66 μmol·L-1, with an overall median value of (24.63±12.97) μmol·L-1. Among the 12 cancer cell lines, the mean IC50 of NCTD for two liver cancers (hepatocellular carcinoma cholangiocarcinoma), gastric cancer, prostate cancer, leukemia, central nervous system cancer, renal cancer were lower than the overall mean value. Also, significant differences among various cancer types and individuals with the same cancer were evident. Conclusion: There are remarkable differences in sensitivity towards NCTD among various cancer types and individuals with the same cancer, indicating the individualized sensitive nature of NTCD and the great future prospect for the development of individualized therapies with NTCD. Many cancers show a similar mean IC50 of NCTD with hepatocellular carcinoma and gastric cancers, for which NTCD is effective clinically, suggesting that NTCD could also be effective for all of these cancers.
