Chung Soo-Ho, Lee Hae-Hyeog, Kim Yeon-Suk, Song Kisung, Kim Tae-Hee
Department of Obstetrics and Gynaecology, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea.
Department of Interdisciplinary Program in Biomedical Science, Soonchunhyang University Graduate School, Asan, Republic of Korea.
Arch Med Sci. 2021 Mar 3;19(2):488-498. doi: 10.5114/aoms/111947. eCollection 2023.
Docosahexaenoic acid (DHA) supplementation has been reported to negatively correlate with cancer cell proliferation and tumour development in many cancer types. Although cumulative evidence has demonstrated the apoptotic effect and cytotoxicity of DHA against tumour development in many cell types, the precise cellular and biochemical mechanisms of DHA-induced apoptosis in human endometrial cancer cells have not been investigated.
MTT assay was performed to confirm the degree of apoptosis by combining treatment with DHA and triacsin C in endometrial cancer cell line. The synergistic effects of triacsin C and DHA were identified by performing flowcytometry and immunoblotting analysis.
Combined treatment with DHA and triacsin C significantly induced apoptosis in RL95-2 endometrial carcinoma cells. Combined treatment with 125 μM DHA and 5 μM triacsin C significantly increased the sub-G1 population and apoptotic fragments in endometrial carcinoma cells. It was also demonstrated that DHA and triacsin C induced apoptosis through mitochondrial pathways via caspases-9, -3, and -7 as well as through the extrinsic pathway by activation of caspase-8/BID.
Further elucidation of the apoptotic mechanisms involving DHA treatment with ACS ablation could shed light on possible new treatment strategies for endometrial cancer. In addition, further research into the mechanisms of DHA and triacsin C-induced apoptotic mechanisms may lead to the development of therapeutic strategies for endometrial cancer.
据报道,补充二十二碳六烯酸(DHA)与多种癌症类型中的癌细胞增殖和肿瘤发展呈负相关。尽管累积证据已证明DHA在许多细胞类型中对肿瘤发展具有凋亡作用和细胞毒性,但DHA诱导人子宫内膜癌细胞凋亡的确切细胞和生化机制尚未得到研究。
采用MTT法,通过将DHA与三辛脂酸C联合处理子宫内膜癌细胞系来确认凋亡程度。通过流式细胞术和免疫印迹分析确定三辛脂酸C与DHA的协同作用。
DHA与三辛脂酸C联合处理显著诱导RL95-2子宫内膜癌细胞凋亡。125μM DHA与5μM三辛脂酸C联合处理显著增加了子宫内膜癌细胞中的亚G1期细胞群和凋亡片段。还证明了DHA和三辛脂酸C通过半胱天冬酶-9、-3和-7经由线粒体途径诱导凋亡,以及通过激活半胱天冬酶-8/BID经由外源性途径诱导凋亡。
进一步阐明涉及DHA与ACS消融联合治疗的凋亡机制,可能为子宫内膜癌的潜在新治疗策略提供线索。此外,对DHA和三辛脂酸C诱导凋亡机制的进一步研究可能会推动子宫内膜癌治疗策略的发展。