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自噬抑制增强姜黄素联合光照诱导的氧化应激和人黑色素瘤细胞生长抑制。

Inhibition of Autophagy Enhances Curcumin United light irradiation-induced Oxidative Stress and Tumor Growth Suppression in Human Melanoma Cells.

机构信息

Aviation Medicine Research Laboratory, The General Hospital of the Air Force, Beijing, China.

Department of Dermatology, The General Hospital of the Air Force, Beijing, China.

出版信息

Sci Rep. 2016 Aug 9;6:31383. doi: 10.1038/srep31383.

DOI:10.1038/srep31383
PMID:27502897
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4977547/
Abstract

Malignant melanoma is the most aggressive form of skin carcinoma, which possesses fast propagating and highly invasive characteristics. Curcumin is a natural phenol compound that has various biological activities, such as anti-proliferative and apoptosis-accelerating impacts on tumor cells. Unfortunately, the therapeutical activities of Cur are severely hindered due to its extremely low bioavailability. In this study, a cooperative therapy of low concentration Cur combined with red united blue light irradiation was performed to inspect the synergistic effects on the apoptosis, proliferation and autophagy in human melanoma A375 cell. The results showed that red united blue light irradiation efficaciously synergized with Cur to trigger oxidative stress-mediated cell death, induce apoptosis and inhibit cell proliferation. Meanwhile, Western blotting revealed that combined disposure induced the formation of autophagosomes. Conversely, inhibition of the autophagy enhanced apoptosis, obstructed cell cycle arrest and induced reversible proliferation arrest to senescence. These findings suggest that Cur combined with red united blue light irradiation could generate photochemo-preventive effects via enhancing apoptosis and triggering autophagy, and pharmacological inhibition of autophagy convert reversible arrested cells to senescence, therefore reducing the possibility that damaged cells might escape programmed death.

摘要

恶性黑色素瘤是皮肤癌中侵袭性最强的一种,具有快速增殖和高度侵袭的特点。姜黄素是一种天然酚类化合物,具有多种生物活性,如对肿瘤细胞的抗增殖和促进凋亡作用。然而,由于其极低的生物利用度,姜黄素的治疗活性受到严重阻碍。在本研究中,采用低浓度姜黄素联合红蓝联合光照射的协同治疗方法,观察其对人黑色素瘤 A375 细胞凋亡、增殖和自噬的协同作用。结果表明,红蓝联合光照射有效地协同姜黄素诱导氧化应激介导的细胞死亡,促进细胞凋亡,抑制细胞增殖。同时,Western blot 结果显示,联合处理诱导自噬小体的形成。相反,自噬的抑制增强了细胞凋亡,阻止了细胞周期停滞,并诱导可逆的增殖停滞向衰老。这些发现表明,姜黄素联合红蓝联合光照射可以通过增强细胞凋亡和触发自噬产生光化疗预防作用,而自噬的药理学抑制将可逆的阻滞细胞转化为衰老,从而降低受损细胞可能逃避程序性死亡的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea6/4977547/bbaa23347283/srep31383-f7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea6/4977547/da8aa39a4e02/srep31383-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea6/4977547/bbaa23347283/srep31383-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea6/4977547/a9fe9337c437/srep31383-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea6/4977547/bb9526af66b6/srep31383-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea6/4977547/ed6d76a6302a/srep31383-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea6/4977547/d5bd18fbd710/srep31383-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea6/4977547/eec786a1f182/srep31383-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea6/4977547/da8aa39a4e02/srep31383-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea6/4977547/bbaa23347283/srep31383-f7.jpg

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