Functional Similarity of Anticancer Drugs by MTT Bioassay
Functional Similarity of Anticancer Drugs by MTT Bioassay
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DOI：
10.4172/1948-5956.1000099
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发表时间：
2011-12
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通讯作者：
T. Hiwasa;T. Utsumi;Mari Yasuraoka;Nana Hanamura;H. Shimada;H. Nakajima;M. Kitagawa;Y. Iwadate;K. Goto;A. Takeda;K. Ohtsuka;H. Ariga;M. Takiguchi
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文献类型：
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作者：
T. Hiwasa;T. Utsumi;Mari Yasuraoka;Nana Hanamura;H. Shimada;H. Nakajima;M. Kitagawa;Y. Iwadate;K. Goto;A. Takeda;K. Ohtsuka;H. Ariga;M. Takiguchi
我们制备了稳定或瞬时转染各种肿瘤相关基因的正常或Ha-ras转化的NIH 3 T3细胞。使用MTT测定法将转染的克隆对16种抗癌药物的化学敏感性与亲本对照细胞进行比较。计算转染基因诱导的化疗敏感性变化，并以数字表示为药物化疗敏感性指数（DCI）。在表达C/EBP？的细胞中经常观察到高DCI值（表明耐药性），C/EBP？，p53、p21、PTEN、显性阴性MDM 2、半胱天冬酶、HSP 90、COUP-TF 1和核心蛋白聚糖。相比之下，表达ras、src、erbB 2和钙蛋白酶抑制蛋白的转染子具有低DCI值，表明敏感性增加。因此，可以根据这些基因的表达量预测癌细胞对抗癌药物的敏感性。然后，我们对抗癌药物之间的DCI值进行了回归分析。顺铂、喜树碱、丝裂霉素C和依托泊苷之间的相关系数（r）相对较高，表明这些药物的作用机制相似。阿克拉霉素、长春新碱、紫杉醇和阿糖胞苷的r值较低，表明这些药物中的每一种都具有不同的独特作用。该分析可以为联合化疗方案的设计提供理论依据。
We prepared normal or Ha-ras-transformed NIH3T3 cells transfected stably or transiently with various tumorrelated genes. The chemosensitivity of the transfected clones to 16 anticancer drugs was compared to the parental control cells using the MTT assay. The chemosensitivity changes induced by transfected genes were calculated and expressed numerically as the Drug Chemosensitivity Index (DCI). High DCI values (indicating resistance) were frequently observed in cells expressing C/EBP?, C/EBP?, p53, p21, PTEN, dominant-negative MDM2, caspases, HSP90, COUP-TF1 and decorin. In contrast, transfectants expressing ras, src, erbB2 and calpastatin had low DCI values, indicating increased sensitivity. Thus, it may be possible to predict the sensitivity of cancer cells toward anticancer drugs based on the expression levels of these genes. We then performed a regression analysis of DCI values between anticancer drugs. The correlation coefficients (r) were relatively high between cisplatin, camptothecin, mitomycin C and etoposide, suggesting that the mechanisms of action of these drugs are similar. The r values of aclarubicin, vincristine, taxol and cytarabine were low, suggesting that each of these drugs has a different and unique effect. This analysis may provide a rationale for design of combination chemotherapy regimens.