State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Chengdu, China.
Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
J Dent Res. 2021 Jul;100(7):754-763. doi: 10.1177/0022034521994756. Epub 2021 Mar 11.
Oral mucositis and taste dysfunction are frequently complained by patients with head and neck cancer receiving radiotherapy, challenging the clinical outcome of cancer treatment. Recent studies have indicated the protective role of Wnt/β-catenin signaling in radiation-induced oral mucositis (RIOM) and its pivotal role in the development and self-renewal of taste buds. The current study hypothesizes that lithium chloride (LiCl), a potent activator of the Wnt/β-catenin signaling pathway, can promote the postirradiation restoration of oral mucosa integrity and taste function. To validate this hypothesis, we established a RIOM mouse model and evaluated the treatment efficacy of LiCl on oral mucositis and taste dysfunction in comparison with keratinocyte growth factor (KGF), an agent approved by the US Food and Drug Administration for oral mucositis. The results showed that LiCl alleviated the weight loss and tongue ulceration of RIOM mice, promoted proliferation of basal epithelial cells, and inhibited epithelial-mesenchymal transition in tongue mucosa. More important, elevated taste bud renewal and dysgeusia recovery toward sweetness were observed in RIOM mice treated with LiCl as compared to those treated by KGF. Collectively, our data demonstrate that LiCl can mitigate oral mucositis and rescue taste alteration induced by irradiation, and activation of Wnt/β-catenin signaling may represent a promising therapy to improve the quality of life of patients receiving radiotherapy.
口腔黏膜炎和味觉障碍是头颈部癌症患者接受放疗后经常抱怨的问题，这对癌症治疗的临床效果提出了挑战。最近的研究表明，Wnt/β-catenin 信号通路在放射性口腔黏膜炎（RIOM）中具有保护作用，并且在味觉感受器的发育和自我更新中起关键作用。本研究假设氯化锂（LiCl），一种 Wnt/β-catenin 信号通路的有效激活剂，可促进口腔黏膜辐射后完整性和味觉功能的恢复。为了验证这一假设，我们建立了 RIOM 小鼠模型，并评估了 LiCl 与角质细胞生长因子（KGF）（一种美国食品和药物管理局批准用于口腔黏膜炎的药物）在治疗口腔黏膜炎和味觉障碍方面的疗效。结果表明，LiCl 减轻了 RIOM 小鼠的体重减轻和舌溃疡，促进了基底上皮细胞的增殖，并抑制了舌黏膜的上皮-间充质转化。更重要的是，与 KGF 治疗相比，LiCl 治疗的 RIOM 小鼠味觉感受器更新和对甜味的味觉障碍恢复得到了提高。总之，我们的数据表明，LiCl 可减轻放疗引起的口腔黏膜炎和味觉改变，并激活 Wnt/β-catenin 信号可能代表一种有前途的治疗方法，可提高接受放疗患者的生活质量。
