Раковая наука и терапия

Functional Similarity of Anticancer Drugs by MTT Bioassay

Abstract

Takaki Hiwasa,Takanobu Utsumi, Mari Yasuraoka, Nana Hanamura, Hideaki Shimada, Hiroshi Nakajima, Motoo Kitagawa, Yasuo Iwadate, Ken-ichiro Goto, Atsushi Takeda, Kenzo Ohtsuka, Hiroyoshi Ariga and Masaki Takiguchi

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.