Potential mechanism of NVP-LDE225 combined with radiotherapy for melanoma
10.3760/cma.j.cn113030-20220128-00044
- VernacularTitle:NVP-LDE225与放射联用治疗黑色素瘤的潜在作用机制
- Author:
Xin LIU
1
;
Jiabao XIANG
;
Yao YIN
;
Yizheng WANG
;
Yifei CHEN
Author Information
1. 南华大学衡阳医学院军事科学院研究生培养基地，衡阳 421001
- Keywords:
Melanoma;
Sonic Hedgehog signal pathway;
NVP-LDE225;
Cell cycle;
Radiotherapy
- From:
Chinese Journal of Radiation Oncology
2022;31(10):933-938
- CountryChina
- Language:Chinese
-
Abstract:
Objective: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 G 0 / G 1 phase. Gamma ray irradiation after NVP-LDE225 treatment further inhibited the SHH signal pathway, arrested the melanoma cells in G 2 / 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.
