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Potential mechanism of NVP‐LDE225 combined with radiotherapy for melanoma
Liu Xin1, Xiang Jiabao1, Yin Yao2, Wang Yizheng2, Chen Yifei2
1Graduate Collaborative Training Base of Academy of Military Sciences, Hengyang Medical School, University of South China, Hengyang 421001, China; 2Laboratory of Military Brain Science and Brain‐inspired Computing, Academy of Military Medical Science, Academy of Military Science, Beijing 100000, China
AbstractObjective To explore the potential mechanism and feasibility of sonic hedgehog (SHH) signal pathway inhibitor NVP‐LDE225 combined with radiotherapy in the treatment of melanoma. Methods The Gli1 mRNA expression of the melanoma cells (Melan‐A and SK‐MEL‐2) was detected by qPCR. After treatment with NVP‐LDE225, GDC‐0449 or combined with radiation for 24 hours, the number and activity of Melan‐A and SK‐MEL‐2 were detected by cell counting and CCK‐8 kit. The survival and proliferation ratio of Melan‐A and SK‐MEL‐2 were detected by cell cloning. The changes of cell cycle of melanoma Melan‐A cells were determined by flow cytometry. The levels of the Bax and Caspase3 of Melan‐A apoptosis protein in melanoma cells were detected by Western blot. Results NVP‐LDE225, an inhibitor of Smo, decreased the mRNA expression of Gli1 in the melanoma cells in a dose‐dependent manner, inhibited the proliferation ratio of the melanoma cells, induced apoptosis, and arrested melanoma cells in G0 / G1 phase. Gamma ray irradiation after NVP‐LDE225 treatment further inhibited the SHH signal pathway, arrested the melanoma cells in G2 / M phase, and further increased the inhibitory effect on melanoma cell proliferation. Conclusions NVP‐LDE225, an inhibitor of Smo, can inhibit SHH signal pathway in melanocytes, suppress cell proliferation, and further increases the effect of inhibiting cell proliferation after combining with irradiation. It can be used as a potential drug in combination with radiotherapy in the treatment of melanoma, which is worthy of further study.
Liu Xin,Xiang Jiabao,Yin Yao et al. Potential mechanism of NVP‐LDE225 combined with radiotherapy for melanoma[J]. Chinese Journal of Radiation Oncology, 2022, 31(10): 933-938.
Liu Xin,Xiang Jiabao,Yin Yao et al. Potential mechanism of NVP‐LDE225 combined with radiotherapy for melanoma[J]. Chinese Journal of Radiation Oncology, 2022, 31(10): 933-938.
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