Overexpression of Ras-Related C3 Botulinum Toxin Substrate 2 Radiosensitizes Melanoma Cells In Vitro and In Vivo
Authors: Shuxian Pan
Hailong Pei
Jing Nie
Anqing Wu
Tom K Hei
Ziyang Guo
Lin Zhu
Yoshiya Furusawa
Wentao Hu
Weiwei Pei
Bingyan Li
Teruaki Konishi
Guangming Zhou
Journal: Oxidative Medicine and Cellular Longevity (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Radioresistance; Radiotherapy; Malignant melanoma; Radiosensitivity; Ras-related C3 botulinum toxin substrate 2
Affiliations: State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China., Medical College of Soochow University, Suzhou 215123, China., Department of Basic Medical Sciences for Radiation Damages, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan., Center for Radiological Research, College of Physician and Surgeons, Columbia University, New York, NY 10032, USA.

Abstract:  Radioresistance is the major obstacle in the radiotherapy of the malignant melanoma. Thus, it is of importance to increase the radiosensitivity of melanoma cells. In the present study, the radioresistant melanoma cell line OCM-1 with inducible overexpression of Ras-related C3 botulinum toxin substrate 2 was established based on a radiation-inducible early growth response gene (Egr-1) promoter. The effects of Ras-related C3 botulinum toxin substrate 2 overexpression on the radiosensitivity of melanoma cells exposed to either X-rays or carbon ion beams were evaluated in cultured cells as well as xenograft tumor models. In addition, both reactive oxygen species yield and the NADPH oxidase activity were measured in the irradiated melanoma cells. It was found that the radiation-inducible overexpression of Ras-related C3 botulinum toxin substrate 2 sensitized the melanoma cells to both X-rays and carbon ion irradiation by enhancing the NADPH oxidase activity and the subsequent reactive oxygen species production. Besides, the overexpression of Ras-related C3 botulinum toxin substrate 2 enhanced the tumor-killing effect of radiotherapy in xenograft tumors significantly. The results of this study indicate that Ras-related C3 botulinum toxin substrate 2 is promising in increasing the radiosensitivity of melanoma cells, which provides experimental evidence and theoretical basis for clinical radiosensitization of the malignant melanoma. 

Retracted: No

PubPeer comments:
 Figure 6. Control tumors too large.  All mice were maintained in the SPF Animal Laboratory of Soochow University. All animal studies were reviewed and approved by the Soochow University Institutional Animal Care and Use Committee.  , 
 Thank you for your valuable comment. All long diameters of the tumors were no longer than 2 cm, and their volumes were below 4.2 cm$3$, not exceeding the recommendations of the University of Pennsylvania Institutional Animal Care and Use Committee guidelines (as follows). Besides, the tumor diameters were measured before the mice were euthanized, leading to the calculated volumes a little bigger than the true volumes, as indicated by the differences between the calculated tumor volumes and the measured tumor weights.   Hopefully our explanations are helpful. , 
 #1 Dr.Wentao Hu, one of our co-authors, has responded as following. Thank you for your valuable comment. All long diameters of the tumors were no longer than 2 cm, and their volumes were below 4.2 cm3, not exceeding the recommendations of the University of Pennsylvania Institutional Animal Care and Use Committee guidelines (as follows). Besides, the tumor diameters were measured before the mice were euthanized, leading to the calculated volumes a little bigger than the true volumes, as indicated by the differences between the calculated tumor volumes and the measured tumor weights. ,