Center of Reproductive Medicine, First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.
Department of Pathology, Jinan University School of Medicine, Guangzhou, 510632, China.
BMC Cancer. 2024 Aug 28;24(1):1060. doi: 10.1186/s12885-024-12848-9.
It is challenging to improve the effects of chemotherapy and reduce its adverse impact on the ovaries. Our previous study suggested that the combination of galaxamide could enhance the antitumor effect of cisplatin (CIS) in HeLa cell xenograft mice. However, their potential effects on ovarian tissues remain unknown.
The Hela tumor-bearing female BALB/c mice model was established and randomly divided into three groups: control group (PBS group), CIS group (0.3 mg/kg CIS group) and galaxamide group (0.3 mg/kg CIS + 3 mg/kg galaxamide-treated group). The serum sex hormones levels, ovarian morphology, functional and molecular characterisation were determined and compared with those of the control group.
The hormonal effects indicated premature ovarian insufficiency (POI) associated with CIS-induced tumor-bearing mice. CIS induces the apoptosis in primordial and developing follicles and subsequently increases follicular atresia, eventually leading to follicle loss. After cotreatment, galaxamide significantly increased anti-Mullerian hormone (AMH) and follicle-stimulating hormone receptor (FSHR) expression and prevented the CIS-induced PI3K pathway, which triggers follicle activation, apoptosis or atresia.
These findings demonstrate that galaxamide could attenuate CIS-induced follicle loss by acting on the PI3K signaling pathway by stimulating AMH and/or FSHR and thus provides promising therapeutic options for patients with cervical cancer.
提高化疗效果并降低其对卵巢的不良影响具有挑战性。我们之前的研究表明，加兰酰胺的联合应用可以增强顺铂（CIS）在 HeLa 细胞异种移植小鼠中的抗肿瘤作用。然而，它们对卵巢组织的潜在影响尚不清楚。
建立荷 HeLa 肿瘤的雌性 BALB/c 小鼠模型，并将其随机分为三组：对照组（PBS 组）、CIS 组（0.3mg/kg CIS 组）和加兰酰胺组（0.3mg/kg CIS+3mg/kg 加兰酰胺处理组）。测定血清性激素水平、卵巢形态、功能和分子特征，并与对照组进行比较。
激素作用表明 CIS 诱导的荷瘤小鼠出现卵巢早衰（POI）。CIS 诱导原始和发育中的卵泡凋亡，随后增加卵泡闭锁，最终导致卵泡丢失。加兰酰胺联合治疗后，抗苗勒管激素（AMH）和卵泡刺激素受体（FSHR）的表达显著增加，并阻止了 CIS 诱导的 PI3K 通路，该通路触发卵泡激活、凋亡或闭锁。
这些发现表明，加兰酰胺通过刺激 AMH 和/或 FSHR 作用于 PI3K 信号通路，可减轻 CIS 诱导的卵泡丢失，为宫颈癌患者提供了有前途的治疗选择。
