Department of Gynecological Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, 310022, Zhejiang, China.
Department of Oncology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, No. 453 Stadium Road, Hangzhou, 310007, Zhejiang, China.
Eur J Med Res. 2024 Aug 5;29(1):405. doi: 10.1186/s40001-024-01968-4.
High-grade serous ovarian cancer (HGSOC) is a common gynecologic malignancy with a poor prognosis. The traditional Chinese medicine formula Erzhimaoling decoction (EZMLD) has anticancer potential. This study aims to elucidate the anticancer effects of EZMLD on HGSOC in vitro and in vivo.
EZMLD-containing serum was prepared from Sprague-Dawley rats for treating SKOV3 ovarian cancer cells at varying concentrations for 24 h and 48 h to determine the IC. Concentrations of 0%, 5%, and 10% for 24 h were chosen for subsequent in vitro experiments. The roles of METTL3 and METTL14 in SKOV3 cells were explored by overexpressing these genes and combining EZMLD with METTL3/14 knockdown. Investigations focused on cell viability and apoptosis, apoptosis-related protein expression, and KRT8 mRNA m6A modification. For in vivo studies, 36 BALB/c nude mice were divided into six groups involving EZMLD (6.75, 13.5, and 27 g/kg) and METTL3 or METTL14 knockdowns, with daily EZMLD gavage for two weeks.
In vitro, EZMLD-containing serum had IC values of 8.29% at 24 h and 5.95% at 48 h in SKOV3 cells. EZMLD-containing serum decreased SKOV3 cell viability and increased apoptosis. EZMLD upregulated METTL3/14 and FAS-mediated apoptosis proteins, while downregulating Keratin 8 (KRT8). EZMLD increased KRT8 mRNA m6A methylation. METTL3/14 overexpression reduced SKOV3 cell viability and increased apoptosis, while METTL3/14 knockdown mitigated EZMLD's effects. In vivo, EZMLD suppressed SKOV3 xenografts growth, causing significant apoptosis and modulating protein expression.
EZMLD has therapeutic potential for ovarian cancer and may be considered for other cancer types. Future research may explore its broader effects beyond cell apoptosis.
高级别浆液性卵巢癌（HGSOC）是一种常见的妇科恶性肿瘤，预后较差。中药方剂二至马灵汤（EZMLD）具有抗癌作用。本研究旨在探讨 EZMLD 在体外和体内对 HGSOC 的抗癌作用。
用含 EZMLD 的 SD 大鼠血清处理 SKOV3 卵巢癌细胞，不同浓度作用 24 h 和 48 h 以确定 IC。选择 0%、5%和 10%的浓度进行后续的体外实验。通过过表达这些基因并结合 EZMLD 与 METTL3/14 敲低来研究 METTL3 和 METTL14 在 SKOV3 细胞中的作用。研究重点是细胞活力和凋亡、凋亡相关蛋白表达以及 KRT8 mRNA m6A 修饰。在体内研究中，将 36 只 BALB/c 裸鼠分为 EZMLD（6.75、13.5 和 27 g/kg）和 METTL3 或 METTL14 敲低组，每天腹腔内注射 EZMLD 两周。
体外，含 EZMLD 的血清在 SKOV3 细胞中 24 h 的 IC 值为 8.29%，48 h 的 IC 值为 5.95%。含 EZMLD 的血清降低了 SKOV3 细胞活力，增加了细胞凋亡。EZMLD 上调了 METTL3/14 和 FAS 介导的凋亡蛋白，同时下调了角蛋白 8（KRT8）。EZMLD 增加了 KRT8 mRNA m6A 甲基化。METTL3/14 过表达降低了 SKOV3 细胞活力，增加了细胞凋亡，而 METTL3/14 敲低则减轻了 EZMLD 的作用。体内，EZMLD 抑制了 SKOV3 异种移植瘤的生长，导致明显的细胞凋亡并调节蛋白表达。
EZMLD 对卵巢癌具有治疗潜力，可能适用于其他癌症类型。未来的研究可能会探索其在细胞凋亡以外的更广泛的作用。
