Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021, Jinan, China.
Department of Oral and Maxillofacial Surgery, College of Stomatology, Guangxi Medical University, 530000, Nanning, China.
Head Face Med. 2022 May 6;18(1):15. doi: 10.1186/s13005-022-00318-1.
Adenoid cystic carcinoma (ACC) is one of the most common malignant salivary gland tumors. Moreover, the unique biological characteristics and complex structures of ACC contribute to its poor survival rates. Recently, proteasome inhibitors have been shown to elicit satisfactory therapeutic effects in the treatment of certain solid tumors, but few studies have been implemented to investigate the effects of proteasome inhibitor therapy for ACC.
In this present study, cell counting kit-8 assay and flow cytometry assay were performed to examine the effects of proteasome inhibitor (MG132) on cell viability and apoptosis. We applied western blot and immunofluorescence staining to explore the expression of the Nrf2/Keap1 signaling pathway and P62, additionally Nrf2 inhibitor (ML385) was utilized to evaluate the role of Nrf2/Keap1 signaling pathway in MG132-induced cell apoptosis.
Our data indicated that MG132 significantly suppressed the growth of ACC-83 cells(MG132 10µM P = 0.0046; 40µM P = 0.0033; 70µM P = 0.0007 versus control) and induced apoptosis (MG132 10µM P = 0.0458; 40µM P = 0.0018; 70µM P = 0.0087 versus control). The application of MG132 induced the up-regulation of Nrf2/Keap1 signaling pathway. Furthermore, inhibition of Nrf2 attenuated the therapeutic effects of MG132 for ACC (both ML385 + MG132 10µM P = 0.0013; 40µM P = 0.0057; 70µM P = 0.0003 versus MG132). P < 0.05 was considered statistically significant.
Our results revealed that proteasome inhibitors MG132 could inhibit the cell viability and induce the apoptosis of ACC through Nrf2/Keap1 signaling pathway.
腺样囊性癌（ACC）是最常见的恶性涎腺肿瘤之一。此外，ACC 独特的生物学特性和复杂的结构导致其生存率较差。最近，蛋白酶体抑制剂已被证明在治疗某些实体瘤方面具有令人满意的治疗效果，但很少有研究探讨蛋白酶体抑制剂治疗 ACC 的效果。
本研究采用细胞计数试剂盒-8 检测法和流式细胞术检测蛋白酶体抑制剂（MG132）对细胞活力和凋亡的影响。我们应用 Western blot 和免疫荧光染色来探讨 Nrf2/Keap1 信号通路和 P62 的表达，此外，还使用 Nrf2 抑制剂（ML385）来评估 Nrf2/Keap1 信号通路在 MG132 诱导的细胞凋亡中的作用。
我们的数据表明，MG132 显著抑制 ACC-83 细胞的生长（MG132 10µM P=0.0046；40µM P=0.0033；70µM P=0.0007 与对照组相比）并诱导凋亡（MG132 10µM P=0.0458；40µM P=0.0018；70µM P=0.0087 与对照组相比）。MG132 的应用诱导了 Nrf2/Keap1 信号通路的上调。此外，抑制 Nrf2 减弱了 MG132 对 ACC 的治疗作用（ML385+MG132 10µM P=0.0013；40µM P=0.0057；70µM P=0.0003 与 MG132 相比）。P<0.05 被认为具有统计学意义。
我们的结果表明，蛋白酶体抑制剂 MG132 可以通过 Nrf2/Keap1 信号通路抑制 ACC 细胞的活力并诱导其凋亡。
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