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Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
In Vitro Assessment of Antitumor Potential and Combination Effect of Classical and Molecular-targeted Anticancer
Yosuke Iijima1, Kenjiro Bandow2, Motohiko Sano3
1Department of Oral and Maxillofacial Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan yoiijima@saitama-med.ac.jp sakagami@dent.meikai.ac.jp.
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.
Insights
Classical anticancer drugs generally show higher antitumor activity than molecular-targeted drugs. Taxanes and gemcitabine exhibit the best tumor specificity, aiding in developing effective cancer treatment regimens.
Area of Science:
- Oncology
- Pharmacology
- Cancer Biology
Background:
- Oral squamous cell carcinoma (OSCC) presents a significant challenge in cancer treatment.
- Evaluating the efficacy of various anticancer drugs is crucial for optimizing therapeutic strategies.
Purpose of the Study:
- To assess the antitumor potential of classical and molecular-targeted anticancer drugs.
- To investigate the combination effects of these chemotherapeutic agents.
- To determine drug efficacy against oral cancer cell lines and normal oral cells.
Main Methods:
- Cytotoxicity assays were performed on four human OSCC cell lines and five human normal oral cell lines using 20 anticancer drugs.
- Cell cycle progression was analyzed using a cell sorter.
- Combination effects were evaluated using the combination index.
Main Results:
- Classical anticancer drugs demonstrated superior antitumor activity compared to most molecular-targeted drugs, with notable exceptions like bortezomib.
- Taxanes and gemcitabine exhibited the highest tumor-specificity (TS) and potency-selectivity expression (PSE) values among classical drugs.
- Combinations of drugs often resulted in additive or antagonistic effects. Certain drugs induced specific cell cycle arrests, while others showed significant toxicity to keratinocytes.
Conclusions:
- The study highlights the differential efficacy of classical versus molecular-targeted anticancer drugs in OSCC.
- A tumor-specificity monitoring system can provide valuable insights for designing effective cancer treatment regimens.
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