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: Dan Chen
Dan Zhao
Yadong Li
Ningbo Zhao
Kai Yang
Journal: Drug Design Development and Therapy (2013)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: adverse reactions; chronochemotherapy; circadian rhythm; efficacy; oral cancer
Affiliations: Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China. 

Abstract:  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. 

Retracted: No

PubPeer comments:
 Figure 1 of this paper shows tumor formation after injection of an oral squamous cell carcinoma cell line, Tca8113, into the cheeks of mice. This photo appears to show an overlap with Figure 1 of another paper by the same research group, i.e. Ningbo Zhao et al.,  Circadian rhythm characteristics of oral squamous cell carcinoma growth in an orthotopic xenograft model , OncoTargets and Therapy 2013:6 41u201346, DOI: 10.2147 OTT.S39955. See: https: pubpeer.com publications 554170547631F699741F9B88913EBF In the Zhao paper, Figure 1 shows tumor formation after injection of a human oral squamous cell carcinoma cell line BcaCD885 into the cheeks of mice. Could the authors please clarify which carcinoma cell line was injected? ![file] , 
 #1 Thank you for pointing it out. We have checked the manuscript and our original data. We confirm that the injected cell in this study was human oral squamous cell carcinoma cell line Tca8113, which was the same as described in the paper, and the cell line was free of errors. However, there is indeed a mistake in Figure 1 in the paper. This is because we inadvertently misplaced a picture of another experiment conducted by our research group at the same time (namely the experimental picture of injection of human oral squamous cell carcinoma cell line BcaCD885). So Figure 1 in this paper overlaps with Figure 1 in another paper of our research group (Ningbo Zhao et al.,  Circadian rhythm characteristics of oral squamous cell carcinoma growth in an orthotopic xenograft model , OncoTargets and Therapy 2013:6 41u201346, DOI: 10.2147 OTT.S39955). We confirm that the error in Figure 1 in this paper does not affect any the results and conclusions of this study. We have contacted the Editorial Office of the magazine to make correction with the correct picture. , 
 Thank you, Dr. Yang, for checking. , 
 Correction, December 2020, found here: https: www.dovepress.com corrigendum-the-drug-efficacy-and-adverse-reactions-in-a-mouse-model-o-peer-reviewed-fulltext-article-DDDT  *The authors have advised due to an error at the time of figure assembly, Figure 1 on page 514 is incorrect. The correct Figure 1 is shown below. The authors apologize for this error and advise it does not affect the results of the paper.* New Figure: ![file] I thank the authors and the journal for addressing this error. ,