Anticancer research · 2019
In Vitro Assessment of Antitumor Potential and Combination Effect of Classical and Molecular-targeted Anticancer Drugs.
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Iijima Yosuke, Bandow Kenjiro, Sano Motohiko, Hino Shunsuke, Kaneko Takahiro, Horie Norio, Sakagami Hiroshi
Аннотация
BACKGROUND/AIM: The aim of the study was to evaluate the antitumor potential and combination effects of chemotherapeutic drugs.
MATERIALS AND METHODS: The cytotoxicity of 20 drip-type classical and molecular-targeted anticancer drugs was examined against 4 human oral squamous cell carcinoma cell lines and 5 human oral normal mesenchymal and epithelial cells. Cell cycle progression was monitored by a cell sorter. Combination effect was evaluated by combination index.
RESULTS: Most of the classical anticancer drugs showed much higher antitumor activity than molecular-targeted drugs, except bortezomib. Among 12 classical anticancer drugs, taxanes and gemsitabine showed the highest tumor-specificity (TS) and potency-selectivity expression (PSE) values, whereas platinum analogs showed the least TS value. Combination of two classical or a classical and a molecular-targeted drug showed mostly additive or antagonistic effect. 5-FU and cisplatin did not produce a subG1 population, but induced G2/M or G1/S arrest, regardless of the addition of cetuximab. Cetuximab, nibolumab and bortezomib showed potent keratinocyte toxicity.
CONCLUSION: The present TS monitoring system may provide useful information for building up the treatment regimens of anticancer drugs.
MATERIALS AND METHODS: The cytotoxicity of 20 drip-type classical and molecular-targeted anticancer drugs was examined against 4 human oral squamous cell carcinoma cell lines and 5 human oral normal mesenchymal and epithelial cells. Cell cycle progression was monitored by a cell sorter. Combination effect was evaluated by combination index.
RESULTS: Most of the classical anticancer drugs showed much higher antitumor activity than molecular-targeted drugs, except bortezomib. Among 12 classical anticancer drugs, taxanes and gemsitabine showed the highest tumor-specificity (TS) and potency-selectivity expression (PSE) values, whereas platinum analogs showed the least TS value. Combination of two classical or a classical and a molecular-targeted drug showed mostly additive or antagonistic effect. 5-FU and cisplatin did not produce a subG1 population, but induced G2/M or G1/S arrest, regardless of the addition of cetuximab. Cetuximab, nibolumab and bortezomib showed potent keratinocyte toxicity.
CONCLUSION: The present TS monitoring system may provide useful information for building up the treatment regimens of anticancer drugs.
Предметные рубрики MeSH
Antineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBortezomibCarcinoma, Squamous CellCell CycleCell Line, TumorCetuximabDeoxycytidineDrug Screening Assays, AntitumorEpithelial CellsFibroblastsFluorouracilHormesisHumansIn Vitro TechniquesKeratinocytesMolecular Targeted TherapyMouth MucosaMouth NeoplasmsNivolumabPlatinum CompoundsTaxoidsGemcitabine