De Luca Arianna, Zavaglia Lucia, Vuono Lucia Francesca, Giordano Francesca, La Padula Davide, De Amicis Francesca, Pezzi Vincenzo, Chimento Adele
Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Rende, Cosenza, Italy.
Department of Health Sciences, "Magna Graecia" University of Catanzaro, Catanzaro, Italy.
J Cell Mol Med. 2025 Aug;29(16):e70786. doi: 10.1111/jcmm.70786.
Leydig cell tumours (LCTs) are uncommon stromal neoplasms of the testis, accounting for less than 3% of all gonadal cancers. Most of them are benign, but the malignant ones are very aggressive without specific effective treatment. Several studies reported pharmacologic insight into the use of statins as anti-tumour agents, but their efficacy on LCTs has not been investigated. Previously, we emphasised the central role of insulin-like growth factor 1 (IGF1)/insulin-like growth factor 1 receptor (IGF1R) signalling in Leydig cell tumorigenesis; here, we showed that simvastatin reduces cell proliferation, determines cell cycle arrest at the G1 phase, and induces reactive oxygen species (ROS) accumulation and apoptosis in R2C and LC540 rat Leydig tumour cells. Furthermore, it prevents isoprenoid farnesyl pyrophosphate (FPP) formation and decreases IGF1R expression, leading to the breakdown of the IGF1R signalling pathway. Importantly, we observed that simvastatin synergised with cisplatin in reducing tumour cell proliferation. Collectively, these data suggest that simvastatin is a potential anticancer drug capable of counteracting LCT growth, and it could be proposed as an adjuvant for chemotherapy in LCT treatment.
睾丸间质细胞瘤（LCTs）是一种罕见的睾丸间质肿瘤，占所有性腺癌的比例不到3%。其中大多数是良性的，但恶性肿瘤具有很强的侵袭性，且没有特效治疗方法。几项研究报告了对他汀类药物作为抗肿瘤药物的药理学见解，但尚未研究其对LCTs的疗效。此前，我们强调了胰岛素样生长因子1（IGF1）/胰岛素样生长因子1受体（IGF1R）信号通路在睾丸间质细胞瘤发生中的核心作用；在此，我们发现辛伐他汀可减少细胞增殖，使细胞周期停滞在G1期，并诱导R2C和LC540大鼠睾丸间质肿瘤细胞中活性氧（ROS）积累和细胞凋亡。此外，它可阻止类异戊二烯法尼基焦磷酸（FPP）的形成，并降低IGF1R表达，导致IGF1R信号通路的中断。重要的是，我们观察到辛伐他汀与顺铂协同作用可降低肿瘤细胞增殖。总体而言，这些数据表明辛伐他汀是一种能够对抗LCT生长的潜在抗癌药物，可作为LCT治疗中化疗的辅助药物。
