Circadian rhythm characteristics of oral squamous cell carcinoma growth in an orthotopic xenograft model
Authors: Hong Tang
Kai Yang
Ningbo Zhao
Dan Chen
Journal: OncoTargets and Therapy (2013)
Discipline: CLINICAL MEDICINE
Keywords: apoptosis; oral carcinoma; proliferation.
Affiliations: Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Abstract:  Background: Recent studies show that circadian rhythm changes are closely related to the occurrence and development of various tumors, such as breast, liver, and prostate. However, there are significant differences in circadian rhythm between different tumors. At present, the circadian rhythm characteristics of oral cancer remain unknown. The purpose of this study is to investigate the circadian rhythm characteristics of the in vivo growth of oral squamous cell carcinoma (OSCC). Materials and methods: Thirty-two nude mice were placed under 12-hour light/12-hour dark cycles. The human OSCC cell line BcaCD885 was inoculated in the cheek of nude mice. After 3 weeks, eight mice were sacrificed at four time points, including 4 hours after light onset (HALO), 10 HALO, 16 HALO, and 22 HALO, during a period of 24 hours. The volume of excised tumors was measured and the proliferative index (PI) and apoptotic index (AI) of tumor cells were determined by flow cytometry. A cosine analysis method was used to determine whether the tumor volume, PI, and AI obeyed a circadian rhythm. Results: There was a significant circadian rhythm in the tumor volume and PI of OSCC cells. For the tumor volume, there were significant differences between the four time points. The peak and trough values of the tumor volume appeared at 3.23 HALO and 15.23 HALO, whereas the peak and trough values of PI appeared at 6.60 HALO and 18.16 HALO, respectively. However, there was no circadian rhythm in the AI of tumor cells, despite significant differences between the four time points. Conclusion: This study demonstrates, for the first time, that the tumor volume and PI of in vivo growing OSCC undergo circadian rhythms. These results support the assertion that time factor should be considered in the occurrence, development, treatment, efficacy evaluation and pathophysiology of OSCC. 

Retracted: No

PubPeer comments:
 Figure 1 of this paper shows tumor formation after injection of a human oral squamous cell carcinoma cell line BcaCD885 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. Kai Yang et al.,  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 , Drug Des Dev Ther 2013:7 511u2013517, DOI: 10.2147 DDDT.S46323. See: https: pubpeer.com publications 8FC97F59339BB019C019020CBABA14 In the Yang paper, Figure 1 shows tumor formation after injection of oral squamous cell carcinoma cell line Tca8113 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 BcaCD885, which was the same as described in the paper, and the cell line was free of errors. Figure 1 in this paper is also correct, that is, Figure 1 shows tumor formation after injection of a human oral squamous cell carcinoma cell line BcaCD885 into the cheeks of mice. In another paper of our research group (Kai Yang et al.,  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 , Drug Des Dev Ther 2013:7 511u2013517, DOI: 10.2147 DDDT.S46323), we confirmed that the cell we injected was human oral squamous cell carcinoma cell line Tca8113, which was the same as described in the paper, and the cell line was not wrong. However, Figure 1 in this paper is indeed wrong. Because we inadvertently misplaced a picture of tumor formation after injection of human oral squamous cell carcinoma cell line BcaCD885 into the cheeks of mice. That was because those two studies were conducted by our research group at the same time and we made a careless mistake. So Figure 1 in the two papers show an overlap. We have contacted the Editorial Office of the magazine to make correction with the correct picture. We confirm that the errors in Figure 1 do not affect any the results and conclusions of this study. ,