The Application of ATR Kinase Inhibitor AZD۶۷۳۸ in Combination with Radiotherapy for the Treatment of Melanoma
محل انتشار: مجله فیزیک و مهندسی پزشکی، دوره: 12، شماره: 3
سال انتشار: 1401
نوع سند: مقاله ژورنالی
زبان: انگلیسی
مشاهده: 43
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شناسه ملی سند علمی:
JR_JBPE-12-3_006
تاریخ نمایه سازی: 30 دی 1402
چکیده مقاله:
Background: Melanoma is categorized as one of the most malignant, severe, and lethal cancers of the skin. Regarding the lack of efficiency of conventional therapies for most patients, novel therapeutic strategies are strongly required. Objective: The current study aimed to assess the impact of AZD۶۷۳۸- an ATR kinase inhibitor- in combination with ۶ MV X-ray on the human melanoma cell line (A۳۷۵).Material and Methods: In this experimental study, cells were treated with different concentrations of AZD۶۷۳۸ for ۲۴ and ۴۸ h in the presence and absence of radiation (۲ Gy, ۴ Gy, and ۶ Gy). The cell viability and cell proliferation assay were examined in both experimental and control groups by MTT and colony formation techniques, respectively. Results: The results indicated that by increasing the concentration of AZD۶۷۳۸, the cell viability was markedly diminished in all treatment groups. As expected, the cell viability of the cells treated with AZD۶۷۳۸ and radiation was significantly lower than the group treated with AZD۶۷۳۸ alone. Besides, the combinatory treatment significantly decreased cell proliferation in the melanoma cell line. The combination of AZD۶۷۳۸ with radiation resulted in a significant increase in cytotoxicity by a ۵۰% increase in cell death when used at concentrations of ۰.۳ µM, ۱ µM, ۱.۵۱ µM, and ۱.۶۱ µM, respectively. Conclusion: The combination of AZD۶۷۳۸ with radiation possesses a synergistic effect on the reduction of the cell viability and proliferation of melanoma cells. This present study provides insight into the impact of Ataxia Telangiectasia and Rad۳-related kinase (ATR) inhibition on the potential role of this kinase in the suppression of melanoma cell proliferation.
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نویسندگان
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MSc, Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran
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PhD, Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran
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PhD, Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran
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MSc, Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran
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