Effect and mechanism of dabrafenib combined with tremelimumab on melanoma
10.12206/j.issn.2097-2024.202504070
- VernacularTitle:达拉非尼联合曲美布单抗对黑色素瘤的治疗作用及机制研究
- Author:
Xiaosong WANG
1
;
Yunjiao LIU
2
;
Jin ZHOU
2
;
Qianqian ZHANG
2
;
Lingjie MENG
1
Author Information
1. Experimental Animal Center, Zunyi Medical University, Zunyi 563006, China.
2. Department of Pharmacy, Luodian Hospital of Baoshan District, Shanghai 201900, China.
- Publication Type:Originalarticles
- Keywords:
dabrafenib;
tremelimumab;
melanoma;
combination therapy;
mechanism
- From:
Journal of Pharmaceutical Practice and Service
2025;43(10):496-502
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect and mechanism of dabrafenib （DAB） combined with tremelimumab （TREM） on melanoma. Methods The effects of DAB combined with TREM on cell viability, cytotoxicity and cell migration of A375 cells were evaluated by Cell Counting Kit-8 （CCK-8） method, lactate dehydrogenase （LDH） method and scratch assay. The levels of reactive oxygen species （ROS）, adenosine triphosphate （ATP）, malondialdehyde （MDA）, and superoxide dismutase （SOD） were detected to evaluate the effects of combined drugs on oxidative stress and energy metabolism. In addition, A375 tumor-bearing nude mice model was used to evaluate the inhibitory effect of the combined treatment on tumor growth in vivo, and the degree of cell apoptosis and cell proliferation in tumor tissues were analyzed by terminal deoxynucleotidyl transferase-mediated dutP Nick end labeling （TUNEL） and proliferating cell nuclear antigen （PCNA） immunohistochemical staining. Results The combined treatment significantly inhibited the survival rate and migration ability of A375 cells and enhanced the cytotoxicity. The combined intervention also significantly increased ROS level, decreased ATP, SOD and MDA levels. It effectively inhibited tumor growth in tumor-bearing nude mice, increased the apoptosis rate of tumor cells and inhibited cell proliferation. Conclusion DAB combined with TREM may improve the therapeutic effect of melanoma by enhancing oxidative stress, inhibiting energy metabolism, and promoting cell apoptosis. This combination therapy may provide a new therapeutic strategy to overcome the limitations of singledrug therapy.
