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The drug efficacy and adverse reactions in a mouse model of oral squamous cell carcinoma treated with oxaliplatin at different time points during a day

Authors Yang K, Zhao N, Zhao D, Chen D, Li Y

Received 5 April 2013

Accepted for publication 11 May 2013

Published 20 June 2013 Volume 2013:7 Pages 511—517

DOI https://doi.org/10.2147/DDDT.S46323

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3


Kai Yang,1,2 Ningbo Zhao,1 Dan Zhao,1,2 Dan Chen,1 Yadong Li1

1Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 2Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing Medical University, Chongqing, People’s Republic of China


Background: Recent studies have shown that the growth and proliferation of cancer cells in vivo exhibit circadian rhythm, and the efficacy and adverse reactions of platinum-based anticancer drugs administered at different times of the day vary significantly on colon cancer. However, since the circadian rhythms of growth and proliferation of various cancer cells often differ, the question of whether the administration of platinum anticancer drugs at different times of the day exerts significantly different efficacy and adverse effects on oral cancers remains to be elucidated. This study has compared the efficacy and adverse effects of oxaliplatin (L-OHP) administration at different times during a day on oral squamous cell carcinoma in mice and has analyzed cellular circadian rhythms.
Methods: The mouse model for oral squamous cell carcinoma was established in 75 nude mice, housed in a 12 hour light/12 hour dark cycle environment. The mice were randomly divided into five groups; four experimental groups were intravenously injected with L-OHP at four time points within a 24-hour period (4, 10, 16, and 22 hours after lights on [HALO]). The control group was intravenously injected with the same volume of saline. Treatment efficacy and adverse reactions were compared on the seventh day after the injection, at 22 HALO. The existence of circadian rhythms was determined by cosine analysis.
Results: Only injections of L-OHP at 16 and 22 HALO significantly prolonged animal survival time. The adverse reactions in mice injected with L-OHP at 16 and 22 HALO were significantly less than those observed in mice administered L-OHP at 4 and 10 HALO. The cosine fitting curve showed that the survival time and adverse reactions exhibited circadian rhythm.
Conclusion: The time factor should be considered when treating patients with oral squamous cell carcinoma with L-OHP in order to achieve better efficacy, reduce the adverse reactions, and improve the patients’ survival time and quality of life.

Keywords: oral cancer, chronochemotherapy, oxaliplatin, efficacy, adverse reactions, circadian rhythm

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