新的研究可能有助于减轻口腔癌症患者的疼痛-动脉网

New study could help reduce pain in oral cancer patients

dental-tribune 等信源发布 2023-09-14 00:48

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Iveta Ramonaite, Dental Tribune International

Iveta Ramonaite，牙科论坛报国际

Wed. 13. September 2023

结婚。13.2023年9月

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NEW YORK, US: Oral tumours can cause agonising pain and thus greatly impair the quality of life of patients. Researchers from the New York University College of Dentistry (NYU Dentistry) have recently reported that the ORAI1 calcium channel, which is a vital protein that controls calcium entry into cells, plays a key role in oral cancer progression and pain generation.

美国纽约：口腔肿瘤可引起痛苦，从而大大损害患者的生活质量。纽约大学牙科学院（NYU Dentistry）的研究人员最近报道，ORAI1钙通道是控制钙进入细胞的重要蛋白质，在口腔癌进展和疼痛产生中起着关键作用。

The researchers believe that the findings could help develop a new approach to treating oral cancer and reducing associated pain in patients..

研究人员认为，这些发现可能有助于开发一种治疗口腔癌和减少患者相关疼痛的新方法。。

According to the researchers, calcium channels have been shown to contribute to cancer progression, but very few studies to date have examined the role of ORAI1 in not only cancer progression but also pain causation. “Our results show that the ORAI1 channel fuels the growth of oral cancer tumours and produces an abundance of molecules that, once secreted, interact with neurons resulting in an increased sensitivity to pain,” lead author Dr Ga-Yeon Son, a postdoctoral fellow in the Department of Molecular Pathobiology at NYU Dentistry, said in a press release..

研究人员表示，钙通道已被证明有助于癌症进展，但迄今为止很少有研究检查ORAI1不仅在癌症进展中的作用，而且在疼痛原因中的作用。“我们的研究结果表明，ORAI1通道促进口腔癌肿瘤的生长，并产生大量的分子，一旦分泌，与神经元相互作用，导致对疼痛的敏感性增加，”主要作者Ga Yeon Son博士，博士后研究员纽约大学牙科分子病理生物学系在一份新闻稿中说。。

The name “ORAI” pays homage to the Horae sisters who, according to Greek mythology, guarded the gates of heaven at Mount Olympus. Similarly, the researchers view the ORAI1 channel as the guardian of calcium entering the cells.

“ORAI”这个名字向Horae姐妹致敬，根据希腊神话，他们在奥林巴斯山保卫天堂之门。同样，研究人员将ORAI1通道视为钙进入细胞的守护者。

“These calcium channels can be a source of good or bad for cells,” said senior author Dr Rodrigo S. Lacruz, professor of molecular pathobiology at the university. “Calcium entering cells is necessary for many good things, but too much calcium for a long time has the opposite effect,” he explained.

高级作者Rodrigo S.Lacruz博士，大学分子病理生物学教授说：“这些钙通道可能是细胞好坏的来源。他解释说：“进入细胞的钙对于许多好处都是必需的，但长时间过多的钙会产生相反的效果。”。

Study results

研究结果

In the study, the researchers analysed tissue samples obtained from both human oral cancer tumours and healthy tongues. They observed a significant upregulation of the ORAI1 gene, which is responsible for encoding the ORAI1 calcium channel, in the tumour samples. However, ORAI1 gene overexpression was not observed in the healthy tissue..

在该研究中，研究人员分析了从人类口腔癌肿瘤和健康舌头获得的组织样本。他们观察到肿瘤样品中负责编码ORAI1钙通道的ORAI1基因显着上调。然而，在健康组织中未观察到ORAI1基因过表达。。

The researchers then examined human oral cancer cells and discovered that the activation of the ORAI1 channel, as opposed to other calcium channels, triggered a substantial influx of calcium into the cancer cells. This influx, in turn, led to an elevation in the levels of a calcium-dependent enzyme known as matrix metalloproteinase-1 (MMP-1), which is secreted from the cancer cells and is critically involved in carcinogenesis..

研究人员随后检查了人类口腔癌细胞，发现与其他钙通道相反，ORAI1通道的激活引发了大量钙流入癌细胞。反过来，这种流入导致钙依赖性酶（称为基质金属蛋白酶-1（MMP-1））的水平升高，该酶从癌细胞分泌并严重参与致癌作用。。

From left: Co-authors Prof. Rodrigo S. Lacruz and Dr Ga-Yeon Son. (Image: NYU)

从左开始：共同作者Rodrigo S.Lacruz教授和Ga Yeon Son博士。（图片：纽约大学）

After removing the ORAI1 gene from oral cancer cells in animal studies, the researchers noticed that tumours progressed more slowly and were less painful, which caused them to wonder whether the MMP-1 was the messenger relaying pain. They later discovered that the MMP-1-rich fluid surrounding oral cancer cells with ORAI1 induced an increase in action potentials, which are essential for transmitting pain signals..

在动物研究中从口腔癌细胞中去除ORAI1基因后，研究人员注意到肿瘤进展缓慢且疼痛减轻，这导致他们想知道MMP-1是否是信使传递疼痛。他们后来发现口腔癌细胞周围富含MMP-1的液体与ORAI1诱导动作电位增加，这对传递疼痛信号至关重要。。

“This gives us evidence that an abundance of MMP-1 may generate increased sensitivity to pain,” Prof. Lacruz explained.

Lacruz教授解释说：“这为我们提供了证据，证明丰富的MMP-1可能会增加对疼痛的敏感性。

Further experiments also showed that ORAI1 gene overexpression in non-invasive cells transformed the cells into invasive ones. Based on the findings, the researchers will now assess a novel drug delivery method that seeks to block the ORAI1 gene in order to test whether it can help prevent oral cancer progression and pain in patients..

进一步的实验还表明，ORAI1基因在非侵入性细胞中的过表达将细胞转化为侵入性细胞。基于这些发现，研究人员现在将评估一种旨在阻断ORAI1基因的新型药物递送方法，以测试它是否可以帮助预防患者的口腔癌进展和疼痛。。

The study, titled “The Ca2+ channel ORAI1 is a regulator of oral cancer growth and nociceptive pain”, was published on 5 September 2023 in Science Signaling.

这项名为“Ca2+通道ORAI1是口腔癌生长和伤害性疼痛的调节剂”的研究于2023年9月5日在“科学信号”杂志上发表。

Academic research

学术研究

Calcium

钙

Dental pain

牙痛

Oral cancer

口腔癌

Pain management

疼痛管理

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