Department of Medical, Jinan Maternity and Child Care Hospital, Jinan, Shandong, China.
Eur Rev Med Pharmacol Sci. 2018 Jul;22(14):4431-4439. doi: 10.26355/eurrev_201807_15494.
Ovarian cancer is a commonly occurred tumor in females. High motility group box-1 protein (HHMB1) is a chromosome-related protein with multiple functions. A recent study revealed critical roles of HMGB1 in occurrence and progression of ovarian cancer. Sirtuin 1 (SIRT1) is a recently identified novel molecule, which regulates acetylation of HMGB1. Whether SIRT1 is involved in migration, invasion or angiogenesis of ovarian cancer is unclear. This study aims to investigate the role of SIRT1-induced HMGB1 acetylation in migration, invasion, and angiogenesis in ovarian cancer.
In ovarian cancer cell line, SIRT1 expression was potentiated. Western blot and immunofluorescence were used to measure HMGB1 expression, acetylation level, and nuclear translocation. Scratch assay and transwell chamber methods were used to examine cell migration and invasion potency. A mouse model with ovarian cancer cell transplantation was generated to measure induced nitric oxide synthase (iNOs) and CD105 expression.
Compared to adjacent tissues, ovarian cancer tissues had significantly decreased SIRT1 expression. In ovarian cancer cells, SIRT1 over-expression decreased HMGB1 and acetylation levels, and SIRT1 knockdown facilitated HMGB1 expression and acetylation. SIRT1 over-expression also suppressed nuclear translocation of HMGB1. Meanwhile, SIRT1 could suppress, migration and angiogenesis of ovarian cancer cells via HMGB1.
SIRT1 over-expression effectively inhibited HMGB1 expression and acetylation, thus inhibiting ovarian cancer migration, invasion and angiogenesis. HMGB1 modulated behaviors of ovarian cancer via SIRT1. Therefore, SIRT1 might work as a treatment target for managing ovarian cancer migration.
卵巢癌是女性常见的肿瘤。高迁移率族蛋白 B1（HMGB1）是一种具有多种功能的染色体相关蛋白。最近的一项研究揭示了 HMGB1 在卵巢癌发生和进展中的关键作用。Sirtuin 1（SIRT1）是一种新发现的分子，它调节 HMGB1 的乙酰化。SIRT1 是否参与卵巢癌的迁移、侵袭或血管生成尚不清楚。本研究旨在探讨 SIRT1 诱导的 HMGB1 乙酰化在卵巢癌迁移、侵袭和血管生成中的作用。
在卵巢癌细胞系中，增强 SIRT1 的表达。采用 Western blot 和免疫荧光法检测 HMGB1 的表达、乙酰化水平和核转位。划痕实验和 Transwell 小室法检测细胞迁移和侵袭能力。建立卵巢癌细胞移植的小鼠模型，检测诱导型一氧化氮合酶（iNOS）和 CD105 的表达。
与邻近组织相比，卵巢癌组织中 SIRT1 的表达明显降低。在卵巢癌细胞中，SIRT1 过表达降低了 HMGB1 和乙酰化水平，而 SIRT1 敲低促进了 HMGB1 的表达和乙酰化。SIRT1 过表达还抑制了 HMGB1 的核转位。同时，SIRT1 可以通过 HMGB1 抑制卵巢癌细胞的迁移和血管生成。
SIRT1 过表达能有效抑制 HMGB1 的表达和乙酰化，从而抑制卵巢癌的迁移、侵袭和血管生成。HMGB1 通过 SIRT1 调节卵巢癌细胞的行为。因此，SIRT1 可能作为治疗卵巢癌迁移的靶点。
