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冬凌草甲素通过 ATM/CHK2 信号通路诱导宫颈癌细胞凋亡和 DNA 损伤。

Alantolactone Induced Apoptosis and DNA Damage of Cervical Cancer through ATM/CHK2 Signaling Pathway.

机构信息

Department of Gynecology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine.

出版信息

Biol Pharm Bull. 2024;47(7):1255-1264. doi: 10.1248/bpb.b23-00804.

DOI:10.1248/bpb.b23-00804
PMID:38972750
Abstract

Traditional Chinese Medicine, known for its minimal side effects and significant clinical efficacy, has attracted considerable interest for its potential in cancer therapy. In particular, Inula helenium L. has demonstrated effectiveness in inhibiting a variety of cancers. This study focuses on alantolactone (ALT), a prominent compound from Inula helenium L., recognized for its anti-cancer capabilities across multiple cancer types. The primary objective of this study is to examine the influence of ALT on the proliferation, apoptosis, cell cycle, and tumor growth of cervical cancer (CC) cells, along with its associated signaling pathways. To determine protein expression alterations, Western blot analysis was conducted. Furthermore, an in vivo model was created by subcutaneously injecting HeLa cells into nude mice to assess the impact of ALT on cervical cancer. Our research thoroughly investigates the anti-tumor potential of ALT in the context of CC. ALT was found to inhibit cell proliferation and induce apoptosis in SiHa and HeLa cell lines, particularly targeting ataxia-telangiectasia mutated (ATM) proteins associated with DNA damage. The suppression of DNA damage and apoptosis induction when ATM was inhibited underscores the crucial role of the ATM/cell cycle checkpoint kinase 2 (CHK2) axis in ALT's anti-tumor effects. In vivo studies with a xenograft mouse model further validated ALT's effectiveness in reducing CC tumor growth and promoting apoptosis. This study offers new insights into how ALT combats CC, highlighting its promise as an effective anti-cervical cancer agent and providing hope for improved treatment outcomes for CC patients.

摘要

中医药以其副作用小、临床疗效显著而备受关注,其在癌症治疗方面的潜力引起了广泛关注。特别是旋覆花在抑制多种癌症方面表现出了有效性。本研究聚焦于旋覆花中的一种重要化合物——土木香内酯(ALT),它已被证明对多种癌症具有抗癌作用。本研究的主要目的是研究 ALT 对宫颈癌(CC)细胞增殖、凋亡、细胞周期和肿瘤生长的影响,以及其相关信号通路。通过 Western blot 分析来确定蛋白表达的变化。此外,通过将 HeLa 细胞皮下注射到裸鼠中来建立体内模型,以评估 ALT 对宫颈癌的影响。我们的研究深入探讨了 ALT 在 CC 中的抗肿瘤潜力。研究发现,ALT 抑制 SiHa 和 HeLa 细胞系的细胞增殖并诱导细胞凋亡,尤其针对与 DNA 损伤相关的共济失调毛细血管扩张突变(ATM)蛋白。当抑制 ATM 时,DNA 损伤的抑制和凋亡的诱导表明 ATM/细胞周期检查点激酶 2(CHK2)轴在 ALT 的抗肿瘤作用中起着关键作用。利用异种移植小鼠模型进行的体内研究进一步验证了 ALT 降低 CC 肿瘤生长和促进凋亡的有效性。本研究为 ALT 对抗 CC 的机制提供了新的见解,突出了其作为一种有效的抗宫颈癌药物的潜力,为 CC 患者的治疗结果提供了改善的希望。

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