Department of Pharmacy, Hospital 971 of The Navy of Chinese PLA, Qingdao, Shandong 266071, P.R. China.
Department of Burn and Plastic Surgery, Hospital 971 of The Navy of Chinese PLA, Qingdao, Shandong 266071, P.R. China.
Oncol Rep. 2021 Jun;45(6). doi: 10.3892/or.2021.8063. Epub 2021 Apr 28.
The etiology for liver cancer has been clearly defined. Unfortunately, therapeutic approaches for liver cancer are rather limited, and liver cancer is insensitive to chemotherapy and radiotherapy. Traditional Chinese medicine (TCM) has become a promising strategy for cancer treatment as TCM elicits broad spectrum anticancer activity. In the present study, we evaluated the anticancer efficacy of AB4, an extract from the medical herb (Bunge) Regel, in liver cancer and . We found that AB4 readily dose‑ and time‑dependently inhibited liver cancer HepG2 and Huh‑7 cell proliferation and colony formation. Western blot and flow cytometry analyses suggested that AB4 treatment induced liver cancer cell apoptosis. Moreover, these findings could be readily recaptured , in which the AB4 regimen resulted in tumor suppression and cancer cell apoptosis in xenograft tumor‑bearing nude mice. Importantly, we noted that treatment with a Notch signaling inhibitor DAPT produced very similar anticancer efficacy in both HepG2 and Huh‑7 cell lines, and administration of DAPT also efficiently suppressed HepG2 xenograft outgrowth. To this end, we anticipated that AB4 and DAPT may act on the same signaling pathway, probably through inhibition of the Notch pathway. Indeed, we found decreased expression of Notch1 protein, as well as downstream targets Hes1 and Hey1, after AB4 treatment. Immunohistochemistry analysis further confirmed the suppression of Notch signaling in HepG2 xenograft‑bearing mice. Taken together, our study highlighted the anticancer efficacy of AB4 in liver cancer. We also provided preliminary data showing Notch as a therapeutic target of AB4. It would be interesting to investigate the anticancer efficacy of AB4 in other types of cancer with elevated Notch activity.
肝癌的病因已经明确。不幸的是，肝癌的治疗方法相当有限，肝癌对化疗和放疗不敏感。中药（TCM）已成为癌症治疗的一种有前途的策略，因为 TCM 具有广谱抗癌活性。在本研究中，我们评估了 AB4（来自药用植物（Bunge）Regel 的提取物）在肝癌和中的抗癌功效。我们发现 AB4 可轻易地剂量和时间依赖性地抑制肝癌 HepG2 和 Huh-7 细胞的增殖和集落形成。Western blot 和流式细胞术分析表明 AB4 处理诱导肝癌细胞凋亡。此外，这些发现可以在异种移植荷瘤裸鼠中轻易地重现，其中 AB4 方案导致肿瘤抑制和癌细胞凋亡。重要的是，我们注意到 Notch 信号抑制剂 DAPT 在 HepG2 和 Huh-7 细胞系中产生非常相似的抗癌功效，并且 DAPT 的给药也有效地抑制了 HepG2 异种移植的生长。为此，我们预计 AB4 和 DAPT 可能作用于相同的信号通路，可能通过抑制 Notch 通路。事实上，我们发现 AB4 处理后 Notch1 蛋白及其下游靶标 Hes1 和 Hey1 的表达降低。免疫组织化学分析进一步证实了 Notch 信号在 HepG2 异种移植瘤小鼠中的抑制。总之，我们的研究强调了 AB4 在肝癌中的抗癌功效。我们还提供了初步数据，表明 Notch 是 AB4 的治疗靶点。有趣的是，用 Notch 活性升高的其他类型的癌症来研究 AB4 的抗癌功效。
