Iranian journal of basic medical sciences · 2026
Combined cold atmospheric plasma and vemurafenib suppress MITF-P21 signaling and MMP-driven metastasis in cutaneous melanoma.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Yazdani Zahra, Mirzaei Mansooreh, Fattahi Sadegh, Sohbatzadeh Farshad, Abediankenari Saeid, Mousavi Arefe, Mirbabaei Fatemeh, Rostami Zeinab, Golpour Monireh, Rafiei Alireza
Аннотация
OBJECTIVES: This study investigated the anti-tumor efficacy of combined cold atmospheric plasma (CAP) and Vemurafenib (VEM) treatment (CAP plus VEM) in cutaneous melanoma, focusing on the MITF-P21 axis and MMP-driven metastasis.
MATERIALS AND METHODS: The therapeutic effects of CAP and VEM were evaluated using in vitro and in vivo models. B16-F10 melanoma and L929 fibroblast cell lines were used to assess long-term cell proliferation and migration using clonogenic and wound-healing assays. In vivo, melanoma tumors were induced in C57BL/6 mice, followed by treatment with CAP, VEM, or CAP plus VEM. Tumor tissues and major organs were collected for histopathological evaluation and molecular analysis. Gene expression levels of MITF, P21, MMP-2, and MMP-9 were quantified by qRT-PCR in both experimental settings.
RESULTS: CAP and VEM significantly inhibited melanoma cell proliferation and migration, with the CAP plus VEM showing the most pronounced effect. In vitro, all treatments markedly down-regulated MITF, P21, and MMP-2 gene expression (P<0.0001). Histopathological analysis revealed extensive tumor necrosis, reduced cellularity, and improved tissue architecture in the CAP plus VEM group, accompanied by fewer metastatic alterations in major organs. qRT-PCR of tumor tissues confirmed significant down-regulation of MMP-2 and MMP-9 after CAP, VEM, and especially the CAP plus VEM group (P<0.0001). The modest in vivo changes in MITF and P21 may reflect microenvironmental influences.
CONCLUSION: The CAP plus VEM enhances anti-tumor efficacy and suppresses metastasis-related pathways in melanoma, both in vitro and in vivo. This suggests a promising complementary therapeutic strategy.
MATERIALS AND METHODS: The therapeutic effects of CAP and VEM were evaluated using in vitro and in vivo models. B16-F10 melanoma and L929 fibroblast cell lines were used to assess long-term cell proliferation and migration using clonogenic and wound-healing assays. In vivo, melanoma tumors were induced in C57BL/6 mice, followed by treatment with CAP, VEM, or CAP plus VEM. Tumor tissues and major organs were collected for histopathological evaluation and molecular analysis. Gene expression levels of MITF, P21, MMP-2, and MMP-9 were quantified by qRT-PCR in both experimental settings.
RESULTS: CAP and VEM significantly inhibited melanoma cell proliferation and migration, with the CAP plus VEM showing the most pronounced effect. In vitro, all treatments markedly down-regulated MITF, P21, and MMP-2 gene expression (P<0.0001). Histopathological analysis revealed extensive tumor necrosis, reduced cellularity, and improved tissue architecture in the CAP plus VEM group, accompanied by fewer metastatic alterations in major organs. qRT-PCR of tumor tissues confirmed significant down-regulation of MMP-2 and MMP-9 after CAP, VEM, and especially the CAP plus VEM group (P<0.0001). The modest in vivo changes in MITF and P21 may reflect microenvironmental influences.
CONCLUSION: The CAP plus VEM enhances anti-tumor efficacy and suppresses metastasis-related pathways in melanoma, both in vitro and in vivo. This suggests a promising complementary therapeutic strategy.